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NEWBORN SCREENING

SCREEN EARLY TREAT EARLY

BABYSHIELD
TMS FACT
SHEET
As per ACMG Guidelines
(American College of Medical Genetics)

0
BABYSHIELD TMS FACT SHEET

DISORDER FACTSHEET FOR NEWBORN


SCREENING
1. Arginase Deficiency................................................................. 17
What is arginase deficiency? ...................................................................... 18
What causes arginase deficiency?............................................................... 18
If arginase deficiency is not treated, what problems occur? ......................... 19
What is the treatment for arginase deficiency? ............................................ 20
What happens when arginase deficiency is treated?.................................... 22
What causes the arginase enzyme to be absent or not working correctly? .... 22
How is arginase deficiency inherited? ......................................................... 22
Is genetic testing available? ........................................................................ 23
What other testing is available? .................................................................. 23
Can you test during pregnancy?.................................................................. 24
Can other members of the family have arginase deficiency or be carriers? ... 24
Can other family members be tested? .......................................................... 25
Where can Confirmatory Testing be done for this condition? ....................... 25
What is the cost of the confirmatory test? .................................................... 25
How many people have arginase deficiency? .............................................. 25
Does arginase deficiency happen more often in a certain ethnic group?....... 25
Does arginase deficiency go by any other names? ....................................... 26
Where can I find more information? ............................................................ 26

2. Argininosuccinic acid lyase deficiency ..................................... 27


What is ASAL deficiency? .............................................................................. 27
What causes ASAL deficiency? ....................................................................... 28
If ASAL deficiency is not treated, what problems occur?..................................... 29
What is the treatment for ASAL deficiency? ...................................................... 30
What happens when ASAL deficiency is treated? .............................................. 33
What causes the ASAL enzyme to be absent or not working correctly? ................. 33
How is ASAL deficiency inherited? .................................................................. 33
Is genetic testing available? ........................................................................... 34
What other testing is available? ...................................................................... 35
Can you test during pregnancy?...................................................................... 35
Can other members of the family have ASAL deficiency or be carriers? ................ 35
Can other family members be tested? .............................................................. 36
Where can Confirmatory Testing be done for this condition? .............................. 36
What is the cost of the confirmatory test? ......................................................... 36
How many people have ASAL deficiency? ........................................................ 36
Does ASAL deficiency happen more frequently in a certain ethnic group?............. 36
Does ASAL deficiency go by any other names? ................................................. 37
Where can I find more information?................................................................. 37

3. Citrullinemia ........................................................................... 38

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BABYSHIELD TMS FACT SHEET

What is citrullinemia?.................................................................................... 38
What causes citrullinemia? ............................................................................ 39
If citrullinemia is not treated, what problems occur? .......................................... 40
What is the treatment for citrullinemia? ........................................................... 42
What happens when citrullinemia is treated? .................................................... 44
What causes the ASAS enzyme to be absent or not working correctly? ................. 45
How is citrullinemia inherited? ....................................................................... 45
Is genetic testing available? ........................................................................... 46
What other testing is available? ...................................................................... 46
Can you test during pregnancy?...................................................................... 46
Can other members of the family have citrullinemia or be carriers?...................... 46
Can other family members be tested? .............................................................. 47
Where can Confirmatory Testing be done for this condition? .............................. 47
How many people have citrullinemia?.............................................................. 48
Does citrullinemia happen more frequently in a certain ethnic group? .................. 48
Does citrullinemia go by any other names? ....................................................... 48
Where can I find more information?................................................................. 48

4. Homocystinuria ....................................................................... 50
What is homocystinuria? ............................................................................... 50
What causes homocystinuria? ........................................................................ 51
If homocystinuria is not treated, what problems occur? ...................................... 52
What is the treatment for homocystinuria? ....................................................... 53
What happens when homocystinuria is treated?................................................ 55
What causes the CBS enzyme to be absent or not working correctly? ................... 56
How is homocystinuria inherited? ................................................................... 56
Is genetic testing available? ........................................................................... 56
What other testing is available? ...................................................................... 57
Can you test during pregnancy?...................................................................... 57
Can other members of the family have homocystinuria or be carriers?.................. 58
Can other family members be tested? .............................................................. 58
Where can Confirmatory Testing be done for this condition? .............................. 58
How many people have homocystinuria?.......................................................... 59
Does homocystinuria happen more often in a certain ethnic group? ..................... 59
Does homocystinuria go by any other names?................................................... 59
Where can I find more information?................................................................. 59

5. Maple Syrup Urine Disease ...................................................... 60


What is MSUD? ............................................................................................ 60
What causes MSUD? ..................................................................................... 61
If MSUD is not treated, what problems occur? ................................................... 62
What is the treatment for MSUD? .................................................................... 63
What happens when MSUD is treated?............................................................. 65
What causes the BCKAD enzymes to be absent or not working correctly? ............. 65
How is MSUD inherited? ................................................................................ 66
Is genetic testing available? ........................................................................... 66
What other testing is available? ...................................................................... 67
Can you test during pregnancy?...................................................................... 67

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Can other members of the family have MSUD or be carriers?............................... 67


Can other family members be tested? .............................................................. 68
Where can Confirmatory Testing be done for this condition? .............................. 68
How many people have MSUD?....................................................................... 69
Does MSUD happen more frequently in a certain ethnic group? ........................... 69
Does MSUD go by any other names?................................................................ 69
Where can I find more information?................................................................. 69

6. Phenylketonuria ...................................................................... 70
What is PKU? ............................................................................................... 71
What causes PKU? ........................................................................................ 71
If PKU is not treated, what problems occur?...................................................... 72
What is the treatment for PKU? ....................................................................... 72
What happens when PKU is treated? ............................................................... 75
What causes the PAH enzyme to be absent or not working correctly? ................... 76
How is PKU inherited? ................................................................................... 76
Is genetic testing available? ........................................................................... 77
What other testing is available? ...................................................................... 77
Can you test during pregnancy?...................................................................... 77
Can other members of the family have PKU or be carriers? ................................. 77
Can other family members be tested? .............................................................. 78
Where can Confirmatory Testing be done for this condition? .............................. 78
How many people have PKU? ......................................................................... 78
Does PKU happen more frequently in a certain ethnic group?.............................. 78
Does PKU go by any other names? .................................................................. 79
Where can I find more information?................................................................. 79

7. Tyrosinemia, type 1 ................................................................. 80


What is tyrosinemia 1? .................................................................................. 80
What causes tyrosinemia 1? ........................................................................... 81
If tyrosinemia 1 is not treated, what problems occur?......................................... 82
What is the treatment for tyrosinemia 1? .......................................................... 84
What happens when tyrosinemia 1 is treated?................................................... 86
What causes the FAH enzyme to be absent or not working correctly? ................... 86
How is tyrosinemia 1 inherited? ...................................................................... 86
Is genetic testing available? ........................................................................... 87
What other testing is available? ...................................................................... 87
Can you test during pregnancy?...................................................................... 87
Can other members of the family have tyrosinemia 1 or be carriers? .................... 88
Can other family members be tested? .............................................................. 88
Where can Confirmatory Testing be done for this condition? .............................. 88
How many people have tyrosinemia 1? ............................................................ 89
Does tyrosinemia 1 happen more frequently in a certain ethnic group? ................. 89
Does tyrosinemia 1 go by any other names?...................................................... 89
Where can I find more information?................................................................. 89

8. Carnitine transporter deficiency ............................................... 91

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BABYSHIELD TMS FACT SHEET

What is CTD? ............................................................................................... 91


What causes CTD? ........................................................................................ 91
If CTD is not treated, what problems occur? ..................................................... 93
What is the treatment for CTD? ....................................................................... 94
What happens when CTD is treated? ............................................................... 96
What causes the CT enzyme to be absent or not working correctly? ..................... 96
How is CTD inherited?................................................................................... 96
Is genetic testing available? ........................................................................... 97
What other testing is available? ...................................................................... 97
Can you test during pregnancy?...................................................................... 97
Can other members of the family have CTD or be carriers? ................................. 98
Can other family members be tested? .............................................................. 99
Where can Confirmatory Testing be done for this condition? .............................. 99
How many people have CTD? ........................................................................100
Does CTD happen more frequently in a certain ethnic group? ............................100
Does CTD go by any other names? .................................................................100
Where can I find more information?................................................................100

9. Carnitine Acylcarnitine Translocase Deficiency....................... 101


What is CAT deficiency? ...............................................................................101
What causes CAT deficiency? ........................................................................102
If CAT deficiency is not treated, what problems occur? .....................................103
What is the treatment for CAT deficiency? .......................................................104
What happens when CAT deficiency is treated? ...............................................106
What causes the CAT enzyme to be absent or not working correctly? ..................106
How is CAT deficiency inherited?...................................................................106
Is there genetic testing available? ..................................................................107
What other testing is available? .....................................................................108
Can you test during pregnancy?.....................................................................108
Can other members of the family have CAT deficiency or be carriers? .................108
Can other family members be tested? .............................................................109
Where can Confirmatory Testing be done for this condition? .............................110
How many people have CAT deficiency? .........................................................110
Does CAT deficiency happen more often in a certain ethnic group?.....................110
Does CAT deficiency go by any other names? ..................................................110
Where can I find more information?................................................................110

10.Carnitine Palmitoyl Transferase Deficiency, type 1A ................ 111


What is CPT-1A deficiency? ..........................................................................112
What causes CPT-1A? ..................................................................................112
If CPT-1A deficiency is not treated, what problems occur? .................................113
What is the treatment for CPT-1A deficiency? ..................................................114
What happens when CPT-1A deficiency is treated?...........................................116
What causes the CPT-1A enzyme to be absent or not working correctly? .............116
How is CPT-1A deficiency inherited? ..............................................................116
Is genetic testing available? ..........................................................................117
What other testing is available? .....................................................................118
Can you test during pregnancy?.....................................................................118

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BABYSHIELD TMS FACT SHEET

Can other members of the family have CPT-1A or be carriers?............................118


Can other family members be tested? .............................................................119
Where can Confirmatory Testing be done for this condition? .............................120
How many people have CPT-1A deficiency? ....................................................120
Does CPT-1A deficiency happen more frequently in a certain ethnic group? .........120
Does CPT-1A deficiency go by any other names?..............................................120
Where can I find more information?................................................................120

11.Carnitine Palmitoyl Transferase Deficiency, type 2 .................. 122


What is CPT-2 deficiency?.............................................................................122
What causes CPT-2 deficiency? .....................................................................123
If CPT-2 deficiency is not treated, what problems occur? ...................................124
What is the treatment for CPT-2 deficiency? ....................................................126
What happens when CPT-2 deficiency is treated?.............................................128
What causes the CPT-2 enzyme to be absent or not working correctly? ...............128
How is CPT-2 deficiency inherited? ................................................................129
Is there genetic testing available? ..................................................................130
What other testing is available? .....................................................................130
Can you test during pregnancy?.....................................................................130
Can other members of the family have CPT-2 deficiency or be carriers?...............130
Can other family members be tested? .............................................................132
Where can Confirmatory Testing be done for this condition? .............................132
How many people have CPT-2 deficiency?.......................................................132
Does CPT-2 deficiency happen more often in a certain ethnic group? ..................132
Does CPT-2 deficiency go by any other names?................................................132
Where can I find more information?................................................................132

12.Glutaric acidemia, type 2........................................................ 133


What is GA-2? .............................................................................................134
What causes GA-2? ......................................................................................135
If GA-2 is not treated, what problems occur?....................................................136
What is the treatment for GA-2? .....................................................................137
What happens when GA-2 is treated? .............................................................139
What causes the enzyme to be absent or not working correctly? .........................140
How is GA-2 inherited? .................................................................................140
Is genetic testing available? ..........................................................................141
What other testing is available? .....................................................................141
Can you test during pregnancy?.....................................................................141
Can other members of the family have GA-2 or be carriers? ...............................142
Can other family members be tested? .............................................................142
Where can Confirmatory Testing be done for this condition? .............................142
What is the cost of the confirmatory test? ........................................................143
How many people have GA-2? .......................................................................143
Does GA-2 happen more often in a certain ethnic group? ...................................143
Does GA-2 go by any other names? ................................................................143
Where can I find more information?................................................................143

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13.Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency ....... 145


What is LCHADD?........................................................................................145
What causes LCHADD?.................................................................................146
If LCHADD is not treated, what problems occur? ..............................................147
What is the treatment for LCHADD?................................................................148
What happens when LCHADD is treated? ........................................................150
What causes the LCHAD enzyme to be absent or not working properly? ..............151
How is LCHADD inherited? ...........................................................................151
Is genetic testing available? ..........................................................................152
What other testing is available? .....................................................................152
Can you test during pregnancy?.....................................................................152
Can other members of the family have LCHADD or be carriers? ..........................153
Can other family members be tested? .............................................................154
Where can Confirmatory Testing be done for this condition? .............................154
How many people have LCHADD?..................................................................154
Does LCHADD happen more often in a certain ethnic group? .............................154
Does LCHADD go by any other names? ...........................................................154
Where can I find more information?................................................................154

14.Medium chain acyl-CoA dehydrogenase deficiency ................. 156


What is MCADD? .........................................................................................156
What causes MCADD? ..................................................................................157
If MCADD is not treated, what problems occur? ...............................................158
What is the treatment for MCADD? .................................................................159
What happens when MCADD is treated? .........................................................160
What causes the MCAD enzyme to be absent or not working correctly? ...............161
How is MCADD inherited? .............................................................................161
Is genetic testing available? ..........................................................................162
What other testing is available? .....................................................................162
Can you test during pregnancy?.....................................................................162
Can other members of the family have MCADD or be carriers? ...........................162
Can other family members be tested? .............................................................163
Where can Confirmatory Testing be done for this condition? .............................164
What is the cost of the confirmatory test? ........................................................164
How many people have MCADD? ...................................................................164
Does MCADD happen more often in a certain ethnic group?...............................164
Does MCADD go by any other names? ............................................................164
Where can I find more information?................................................................164

15.Short chain acyl-CoA dehydrogenase deficiency ..................... 166


What is SCADD?..........................................................................................166
What causes SCADD?...................................................................................167
If SCADD is not treated, what problems occur? ................................................168
What is the treatment for SCADD? ..................................................................169
What happens when SCADD is treated? ..........................................................171
What causes the SCAD enzyme to be absent or not working properly? ................171
How is SCADD inherited? .............................................................................171

7 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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BABYSHIELD TMS FACT SHEET

Is there genetic testing available? ..................................................................172


What other testing is available? .....................................................................173
Can you test during pregnancy?.....................................................................173
Can other members of the family have SCADD or be carriers? ............................173
Can other family members be tested? .............................................................174
Where can Confirmatory Testing be done for this condition? .............................174
What is the cost of the confirmatory test? ........................................................175
How many people have SCADD? ....................................................................175
Does SCADD happen more frequently in a certain ethnic group? ........................175
Does SCADD go by any other names? .............................................................175
Where can I find more information?................................................................175

16.Short Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency .... 176


What is M/SCHADD? ....................................................................................176
What causes M/SCHADD? .............................................................................177
If M/SCHADD is not treated, what problems occur? ..........................................178
What is the treatment for M/SCHADD? ............................................................179
What happens when M/SCHADD is treated? ....................................................181
What causes the SCHAD enzyme to be absent or not working correctly?..............181
How is M/SCHADD inherited?........................................................................181
Is genetic testing available? ..........................................................................182
What other testing is available? .....................................................................182
Can you test during pregnancy?.....................................................................182
Can other members of the family have M/SCHADD or be carriers? ......................183
Can other family members be tested? .............................................................184
Where can Confirmatory Testing be done for this condition? .............................184
What is the cost of the confirmatory test? ........................................................184
How many people have M/SCHADD? ..............................................................184
Does M/SCHADD happen more frequently in a certain ethnic group? ..................184
Does M/SCHADD go by any other names? .......................................................185
Where can I find more information?................................................................185

17.Trifunctional protein deficiency.............................................. 186


What is TFP deficiency?................................................................................187
What causes TFP deficiency? ........................................................................187
If TFP deficiency is not treated, what problems occur? ......................................188
What is the treatment for TFP deficiency? .......................................................190
What happens when TFP deficiency is treated?................................................193
What causes the trifunctional protein enzyme group to be absent or not working
properly? ....................................................................................................193
How is TFP deficiency inherited? ...................................................................193
Is genetic testing available? ..........................................................................194
What other testing is available? .....................................................................195
Can you test during pregnancy?.....................................................................195
Can other members of the family have TFP deficiency or be carriers?..................195
Can other family members be tested? .............................................................196
Where can Confirmatory Testing be done for this condition? .............................196
How many people have TFP deficiency?..........................................................196

8 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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BABYSHIELD TMS FACT SHEET

Does TFP deficiency happen more often in a certain ethnic group? .....................197
Does TFP deficiency go by any other names?...................................................197
Where can I find more information?................................................................197

18.Very long chain acyl-CoA dehydrogenase ............................... 198


What is VLCADD? ........................................................................................198
What causes VLCADD?.................................................................................199
If VLCADD is not treated, what problems occur? ..............................................200
What is the treatment for VLCADD? ................................................................202
What happens when VLCADD is treated? ........................................................204
What causes the VLCAD enzyme to be absent or not working correctly? ..............205
How is VLCADD inherited?............................................................................205
Is there genetic testing available? ..................................................................206
What other testing is available? .....................................................................206
Can you test during pregnancy?.....................................................................206
Can other members of the family have VLCADD or be carriers? ..........................206
Can other family members be tested? .............................................................207
Where can Confirmatory Testing be done for this condition? .............................207
What is the cost of the confirmatory test? ........................................................208
How many people have VLCADD? ..................................................................208
Does VLCADD happen more frequently in a certain ethnic group? ......................208
Does VLCADD go by any other names? ...........................................................208
Where can I find more information?................................................................208

19.Beta ketothiolase deficiency ................................................... 210


What is BKD? ..............................................................................................210
What causes BKD? .......................................................................................211
If BKD is not treated, what problems occur? ....................................................211
What is the treatment for BKD? ......................................................................213
What happens when BKD is treated? ..............................................................215
What causes the MAT enzyme to be absent or not working correctly? .................215
How is BKD inherited? ..................................................................................215
Is genetic testing available? ..........................................................................216
What other testing is available? .....................................................................216
Can you test during pregnancy?.....................................................................216
Can other members of the family have BKD or be carriers? ................................217
Can other family members be tested? .............................................................217
Where can Confirmatory Testing be done for this condition? .............................218
What is the cost of the confirmatory test? ........................................................218
How many people have BKD? ........................................................................218
Does BKD happen more frequently in a certain ethnic group?.............................218
Does BKD go by any other names? .................................................................218
Where can I find more information?................................................................219

20.Glutaric acidemia, type 1........................................................ 220


What is GA-1? .............................................................................................220
What causes GA-1? ......................................................................................221

9 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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BABYSHIELD TMS FACT SHEET

If GA-1 is not treated, what problems occur?....................................................221


What is the treatment for GA-1? .....................................................................223
What happens when GA-1 is treated? .............................................................226
What causes the glutaryl-CoA dehydrogenase enzyme to be absent or not working
correctly?....................................................................................................226
How is GA-1 inherited? .................................................................................226
Is genetic testing available? ..........................................................................227
What other testing is available? .....................................................................227
Can you test during pregnancy?.....................................................................227
Can other members of the family have GA-1 or be carriers? ...............................228
Can other family members be tested? .............................................................228
Where can Confirmatory Testing be done for this condition? .............................229
What is the cost of the confirmatory test? ........................................................229
How many people have GA-1? .......................................................................229
Does GA-1 happen more frequently in a certain ethnic group? ............................229
Does GA-1 go by any other names? ................................................................229
Where can I find more information?................................................................230

21.Holocarboxylase synthetase deficiency ................................... 231


What is HCSD? ............................................................................................231
What causes HCSD?.....................................................................................232
If HCSD is not treated, what problems occur? ..................................................232
What is the treatment for HCSD? ....................................................................234
What happens when HCSD is treated? ............................................................234
What causes the HCS enzyme to be absent or not working correctly? ..................234
How is HCSD inherited?................................................................................235
Is genetic testing available? ..........................................................................235
What other testing is available? .....................................................................236
Can you test during pregnancy?.....................................................................236
Can other members of the family have HCSD or be carriers? ..............................236
Can other family members be tested? .............................................................237
Where can Confirmatory Testing be done for this condition? .............................237
How many people have HCSD? ......................................................................237
Does HCSD happen more frequently in a certain ethnic group? ..........................237
Does HCSD go by any other names? ...............................................................237
Where can I find more information?................................................................238

22.3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency .................. 239


What is HMG lyase deficiency? ......................................................................240
What causes HMG lyase deficiency? ...............................................................240
If HMG lyase deficiency is not treated, what problems occur? ............................241
What is the treatment for HMG lyase deficiency? ..............................................242
What happens when HMG lyase deficiency is treated? ......................................245
What causes the HMG CoA lyase enzyme to be absent or not working correctly? ..245
How is HMG lyase deficiency inherited?..........................................................245
Is genetic testing available? ..........................................................................246
What other testing is available? .....................................................................247
Can you test during pregnancy?.....................................................................247

10 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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BABYSHIELD TMS FACT SHEET

Can other members of the family have HMG lyase deficiency or be carriers? ........247
Can other family members be tested? .............................................................248
Where can Confirmatory Testing be done for this condition? .............................248
What is the cost of the confirmatory test? ........................................................249
How many people have HMG lyase deficiency? ................................................249
Does HMG lyase deficiency happen more frequently in a certain ethnic group? ....249
Does HMG lyase deficiency go by any other names? .........................................249
Where can I find more information?................................................................249

23.Isobutyryl-CoA Dehydrogenase Deficiency ............................. 250


What is IBD deficiency? ................................................................................250
What causes IBD deficiency? .........................................................................252
If IBD deficiency is not treated, what problems occur? ......................................252
What is the treatment for IBD deficiency? ........................................................253
What happens when IBD deficiency is treated? ................................................255
What causes the enzyme to be absent or not working correctly? .........................255
How is IBD deficiency inherited?....................................................................255
Is genetic testing available? ..........................................................................256
What other testing is available? .....................................................................256
Can you test during pregnancy?.....................................................................257
Can other members of the family have IBD deficiency or be carriers? ..................257
Can other family members be tested? .............................................................258
Where can Confirmatory Testing be done for this condition? .............................258
How many people have IBD deficiency? ..........................................................258
Does IBD deficiency happen more frequently in a certain ethnic group? ..............258
Does IBD deficiency go by any other names? ...................................................258
Where can I find more information?................................................................259

24.Isovaleric Acidemia ............................................................... 260


What is IVA? ...............................................................................................260
What causes IVA? ........................................................................................261
If IVA is not treated, what problems occur? .....................................................262
What is the treatment for IVA? .......................................................................263
What happens when IVA is treated? ...............................................................265
What causes the isovaleryl-CoA dehydrogenase enzyme to be absent or not working
correctly?....................................................................................................265
How is IVA inherited? ...................................................................................266
Is genetic testing available? ..........................................................................266
What other testing is available? .....................................................................267
Can you test during pregnancy?.....................................................................267
Can other members of the family have IVA or be carriers? .................................267
Can other family members be tested? .............................................................268
Where can Confirmatory Testing be done for this condition? .............................268
How many people have IVA? .........................................................................268
Does IVA happen more frequently in a certain ethnic group? .............................268
Does IVA go by any other names? ..................................................................268
Where can I find more information?................................................................269

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25.Methylmalonic Acidemia ........................................................ 270


What is MMA? .............................................................................................270
What causes MMA?......................................................................................270
If MMA is not treated, what problems occur? ...................................................272
What is the treatment for MMA?.....................................................................274
What happens when MMA is treated? .............................................................277
What causes the enzyme to be absent or not working correctly? .........................277
How is MMA inherited?.................................................................................277
Is genetic testing available? ..........................................................................278
What other testing is available? .....................................................................279
Can you test during pregnancy?.....................................................................279
Can other members of the family have MMA or be carriers? ...............................279
Can other family members be tested? .............................................................280
Where can Confirmatory Testing be done for this condition? .............................280
How many people have MMA? .......................................................................280
Does MMA happen more frequently in a certain ethnic group? ...........................280
Does MMA go by any other names? ................................................................280
Where can I find more information?................................................................281

26.Methylmalonic Acidemia with Homocystinuria ........................ 282


What is MMA+HCU?.....................................................................................282
What causes MMA+HCU?..............................................................................283
If MMA+HCU is not treated, what problems occur? ...........................................284
What is the treatment for MMA+HCU?.............................................................286
What happens when MMA+HCU is treated? .....................................................289
What causes the enzyme to be absent or not working correctly? .........................289
How is MMA+HCU inherited? ........................................................................289
Is genetic testing available? ..........................................................................290
What other testing is available? .....................................................................291
Can you test during pregnancy?.....................................................................291
Can other members of the family have MMA+HCU or be carriers? .......................291
Can other family members be tested? .............................................................292
Where can Confirmatory Testing be done for this condition? .............................292
How many people have MMA+HCU with homocystinuria? .................................292
Does MMA+HCU happen more frequently in a certain ethnic group? ...................292
Does MMA+HCU with homocystinuria go by any other names? ..........................292
Where can I find more information?................................................................293

27.Propionic Acidemia ............................................................... 294


What is PA? ................................................................................................294
What causes PA? .........................................................................................295
If PA is not treated, what problems occur?.......................................................296
What is the treatment for PA? ........................................................................297
What happens when PA is treated?.................................................................301
What causes the PCC enzyme to be absent or not working correctly? ..................301
How is PA inherited? ....................................................................................301
Is genetic testing available? ..........................................................................302

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What other testing is available? .....................................................................302


Can you test during pregnancy?.....................................................................302
Can other members of the family have PA or be carriers? ..................................303
Can other family members be tested? .............................................................303
Where can Confirmatory Testing be done for this condition? .............................303
What is the cost of the confirmatory test? ........................................................304
How many people have PA? ..........................................................................304
Does PA happen more frequently in a certain ethnic group? ...............................304
Does PA go by any other names?....................................................................304
Where can I find more information?................................................................304

28.3-methylcrotonyl CoA Carboxylase Deficiency ........................ 306


What is 3MCC deficiency? .............................................................................306
What causes 3MCC deficiency?......................................................................307
If 3MCC deficiency is not treated, what problems occur? ...................................308
What is the treatment for 3MCC deficiency?.....................................................309
What happens when 3MCC deficiency is treated? .............................................311
What causes the 3MCC enzyme to be absent or not working correctly?................312
How is 3MCC deficiency inherited? ................................................................312
Is genetic testing available? ..........................................................................313
What other testing is available? .....................................................................313
Can you test during pregnancy?.....................................................................313
Can other members of the family have 3MCC deficiency or be carriers? ...............313
Can other family members be tested? .............................................................314
Where can Confirmatory Testing be done for this condition? .............................314
What is the cost of the confirmatory test? ........................................................315
How many people have 3MCC deficiency? .......................................................315
Does 3MCC deficiency happen more frequently in a certain ethnic group? ...........315
Does 3MCC deficiency go by any other names? ................................................315
Where can I find more information?................................................................315

29.2-Methylbutyryl CoA Dehydrogenase Deficiency ..................... 316


What is 2MBCD deficiency?...........................................................................316
What causes 2MBCD deficiency? ...................................................................317
If 2MBCD deficiency is not treated, what problems occur? .................................318
What is the treatment for 2MBCD deficiency?...................................................319
What happens when 2MBCD deficiency is treated? ...........................................322
What causes the 2MBCD enzyme to be absent or not working correctly?..............322
How is 2MBCD deficiency inherited? ..............................................................322
Is genetic testing available? ..........................................................................323
What other testing is available? .....................................................................323
Can you test during pregnancy?.....................................................................323
Can other members of the family have 2MBCD deficiency or be carriers? .............324
Can other family members be tested? .............................................................324
Where can Confirmatory Testing be done for this condition? .............................325
What is the cost of the confirmatory test? ........................................................325
How many people have 2MBCD deficiency? .....................................................325
Does 2MBCD deficiency happen more frequently in a certain ethnic group? .........325

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Does 2MBCD deficiency go by any other names? ..............................................326


Where can I find more information?................................................................326

30.Alpha Thalassemia ................................................................ 327


What is alpha thalassemia? ...........................................................................327
What causes alpha thalassemia?....................................................................328
What are the symptoms of alpha thalassemia? .................................................328
What is the treatment for alpha thalassemia? ...................................................330
What causes the decreased production of alpha globin? ....................................331
How is alpha thalassemia inherited?...............................................................331
Is genetic testing available? ..........................................................................332
What other testing is available? .....................................................................332
Can you test during pregnancy?.....................................................................332
Can other members of the family have alpha thalassemia or be carriers? .............333
Can other family members be tested? .............................................................333
Where can Confirmatory Testing be done for this condition? .............................333
The confirmatory test for the diagnosis is done by any of the two different
techniques amongst HPLC, capillary electrophoresis and IEF using whole blood after
six months of age of the patient......................................................................333
Center: .......................................................................................................333
How many people have alpha thalassemia? .....................................................333
Does alpha thalassemia happen more often in a certain ethnic group?.................333
Does alpha thalassemia go by any other names? ..............................................333
Where can I find more information?................................................................334

31.Congenital Adrenal Hyperplasia ............................................. 335


What is CAH?..............................................................................................335
What causes CAH?.......................................................................................336
If CAH is not treated, what problems occur? ....................................................337
What is the treatment for CAH? ......................................................................341
What happens when CAH is treated? ..............................................................344
What causes the21-hydroxylase enzyme to be absent or not working correctly?....344
How is CAH deficiency inherited? ..................................................................344
Is genetic testing available? ..........................................................................345
What other testing is available? .....................................................................346
Can you test during pregnancy?.....................................................................346
Can other members of the family have CAH or be carriers? ................................346
Can other family members be tested? .............................................................347
Where can Confirmatory Testing be done for this condition? .............................347
What is the cost of the confirmatory test? ........................................................347
How many people have CAH? ........................................................................347
Does CAH happen more frequently in a certain ethnic group? ............................348
Does CAH go by any other names? .................................................................348
Where can I find more information?................................................................348

32.Cystic Fibrosis ...................................................................... 350


What is CF? ................................................................................................350

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What causes CF? .........................................................................................351


What are the symptoms of CF?.......................................................................351
What is the treatment for CF? ........................................................................353
What happens when CF is treated?.................................................................356
What causes the CFTR protein to be absent or not working correctly? .................357
How is CF inherited? ....................................................................................357
Is genetic testing available? ..........................................................................358
What other testing is available? .....................................................................358
Can you test during pregnancy?.....................................................................359
Can other members of the family have CF or be carriers?...................................359
Can other family members be tested? .............................................................359
Where can Confirmatory Testing be done for this condition? .............................360
What is the cost of the confirmatory test? ........................................................360
How many people have CF?...........................................................................360
Does CF happen more often in a certain ethnic group? ......................................360
Does CF go by any other names?....................................................................360
Where can I find more information?................................................................360

33.Congenital Hypothyroidism.................................................... 362


What is CH? ................................................................................................362
What causes CH? .........................................................................................363
If CH is not treated, what problems occur? ......................................................364
What is the treatment for CH? ........................................................................365
What happens when CH is treated? ................................................................367
How do I know if my childs CH is inherited? ...................................................367
If my child might have an inherited form of CH, is genetic testing available? ........368
What other testing is available? .....................................................................369
Can you test during pregnancy?.....................................................................369
Can other members of the family have CH?......................................................369
Where can Confirmatory Testing be done for this condition? .............................370
What is the cost of the confirmatory test? ........................................................370
How many people have CH? ..........................................................................370
Does CH happen more frequently in a certain ethnic group? ..............................370
Does CH go by any other names? ...................................................................370
Where can I find more information?................................................................370

34.Glucose-6-Phosphate Dehydrogenase Deficiency .................... 372


What is G6PD deficiency? .............................................................................372
What causes G6PD deficiency? ......................................................................373
If G6PD deficiency is not treated, what problems occur?....................................373
What is the treatment for G6PD deficiency? .....................................................374
What causes the G6PD enzyme to be absent or not working correctly? ................374
How is G6PD deficiency inherited? .................................................................375
Is genetic testing available? ..........................................................................375
What other testing is available? .....................................................................375
Can you test during pregnancy?.....................................................................376
Can other members of the family have G6PD deficiency or be carriers? ...............376
Can other family members be tested? .............................................................376

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How many people have G6PD deficiency? .......................................................377


Does G6PD deficiency happen more often in a certain ethnic group? ...................377
Does G6PD deficiency go by any other names? ................................................377
Where can I find more information?................................................................377

35.Galactosemia ........................................................................ 377


What is galactosemia? ..................................................................................378
What causes galactosemia?...........................................................................378
If galactosemia is not treated, what problems occur? ........................................379
What is the treatment for galactosemia?..........................................................381
What happens when galactosemia is treated? ..................................................383
What causes the GALT enzyme to be absent or not working correctly? ................384
How is galactosemia inherited? .....................................................................384
Is genetic testing available? ..........................................................................385
What other testing is available? .....................................................................386
Can you test during pregnancy?.....................................................................386
Can other members of the family have galactosemia or be carriers? ....................386
Can other family members be tested? .............................................................387
Where can Confirmatory Testing be done for this condition? .............................387
What is the cost of the confirmatory test? ........................................................388
How many people have galactosemia? ............................................................388
Does galactosemia happen more frequently in a certain ethnic group? ................388
Does galactosemia go by any other names? .....................................................388
Where can I find more information?................................................................388

36.Sickle Cell Disease ................................................................ 389


What is SCD? ..............................................................................................389
What causes SCD? .......................................................................................390
What are the symptoms of SCD? ....................................................................390
What is the treatment for SCD? ......................................................................392
What happens when SCD is treated? ..............................................................395
What causes the red blood cells to be sickle-shaped?........................................395
How is SCD inherited? ..................................................................................396
Is genetic testing available? ..........................................................................396
What other testing is available? .....................................................................397
Can you test during pregnancy?.....................................................................397
Can other members of the family have SCD or be carriers? ................................398
Can other family members be tested? .............................................................398
Where can Confirmatory Testing be done for this condition? .............................399
How many people have SCD? ........................................................................399
Does SCD happen more often in a certain ethnic group? ....................................399
Does SCD go by any other names? .................................................................399
Where can I find more information?................................................................399

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A
Can other members of the
rginase Deficiency
family have arginase
deficiency or be carriers?
Can other family members
Acronym: ARG 1 deficiency
be tested?
What is arginase Where can Confirmatory
deficiency? Testing be done for this
What causes arginase condition?
deficiency? What is the cost of the
If arginase deficiency is not confirmatory test?
treated, what problems How many people have
occur? arginase deficiency?
What is the treatment for Does arginase deficiency
arginase deficiency? happen more often in a
What happens when certain ethnic group?
arginase deficiency is Does arginase deficiency go
treated? by any other names?
What causes the arginase Where can I find more
enzyme to be absent or not information?
working correctly?
This fact sheet contains general
How is arginase deficiency
information about arginase deficiency.
inherited?
Every child is different and some of
Is genetic testing available?
these facts may not apply to your child
What other testing is
specifically. Certain treatments may be
available?
recommended for some children but
Can you test during
not others. All children with arginase
pregnancy?
deficiency should be followed by a
metabolic doctor in addition to their
primary doctor.

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What is arginase deficiency? amino acid disorder. People with this


condition have problems removing
Arginase deficiency is one type of
ammonia from the body. Ammonia is a
harmful substance. It is made when
Amino Acid Disorders:
protein and its

Amino acid disorders (AAs) are a


building blocks, amino acids, are
group of rare inherited conditions. They
broken down for use by the body.
are caused by enzymes that do not
work properly.

Protein is made up of smaller building What causes arginase deficiency?


blocks called amino acids. A number of This is one of a small number of amino
different enzymes are needed to process acid disorders called urea cycle
these amino acids for use by the body. disorders (UCD).
Because of missing or non-working
enzymes, people with amino acid
disorders cannot process certain amino
acids. These amino acids, along with
other toxic substances, then build up in
the body and cause problems.

The symptoms and treatment vary


between different amino acid disorders.
They can also vary from person to
person with the same amino acid
disorder. See the fact sheets for each
specific amino acid disorder.

Amino acid disorders are inherited in


an autosomal recessive manner and
affect both males and females.

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It occurs when an enzyme called Episodes of illness caused by high


arginase is either missing or not levels of ammonia in the blood can
working properly. This enzymes job is sometimes occur but are not common.
to help break down the amino acid Some of the first symptoms of high
arginine and to help remove ammonia blood ammonia are:
from the body.

When arginase is not working,


arginine, along with ammonia, can
build up in the blood. This can cause
serious effects on growth, learning and
health.

If arginase deficiency is not treated,


what problems occur?
The effects of this condition vary from
person to person. Symptoms can start
in infancy or not until later in
childhood. Many children have their
first symptoms around one year to
three years of age. Effects in infants
can include:
poor appetite
poor growth excess sleepiness or lack of
learning delays energy
spasticity irritability
poor coordination and balance vomiting
problems
If untreated, other symptoms can
fussiness or illness when fed
follow:
high protein food

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muscle weakness during illness or infection


decreased or increased muscle after high-protein meals
tone
What is the treatment for arginase
breathing problems
deficiency?
problems staying warm
seizures Your babys primary doctor will work
swelling of the brain with a metabolic doctor and a dietician
coma, and sometimes death
to care for your child.

Often, symptoms of arginase deficiency Prompt treatment is needed to prevent


do not begin until later in infancy or the build-up of arginine and ammonia.
childhood. Common effects in older You should start treatment as soon as
infants and children include:
you know your child has the condition.

poor growth The following are treatments often


spasticity recommended for babies and children
small head size
with arginase deficiency:
hyperactivity
behavior problems 1. Low-protein diet and/or special
learning delays medical foods and formula
avoidance of meat or other high Most children need to eat a diet made
protein foods up of very low-protein foods and
occasional bouts of vomiting special medical foods. Your dietician
and excessive sleepiness will create a food plan that contains the
right amount of protein, nutrients, and
Episodes of high blood ammonia,
energy to keep your child healthy. The
described above, happen rarely. If they
food plan should be continued
occur, they are more likely to happen:
throughout your childs life.

after going without food for long


Low-protein diet: one of the main
periods
treatments is a low-protein diet. Foods

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that need to be avoided or limited Your child may be given a special


include: formula that contains the correct
amount of nutrients and amino acids.
milk, cheese and other dairy products
Your metabolic doctor and dietician
meat and poultry
will tell you whether your child should
fish
use this formula and how much to use.
eggs
Some states offer help with payment, or
dried beans and legumes
require private insurance to pay for the
nuts and peanut butter
formula and other special medical
foods.
Eating these foods can cause ammonia
and arginine to build up, resulting in
Your childs exact food plan will
the symptoms described above. Many
depend on many things such as his or
vegetables and fruits have only small
her age, weight, and general health.
amounts of protein and can be eaten in
Your dietician will fine-tune your
carefully measured amounts.
childs diet over time.

Do not remove all protein from the diet.


2. Medication
Your child still needs a certain amount
There are certain medications that can
of protein for normal growth and
help the body get rid of excess arginine
development. Any changes in the diet
and ammonia. Your metabolic doctor
should be made under the guidance of
will decide which medications your
a dietician.
child should take.

Medical foods and formula:


3. Bloodtests:
There are medical foods such as
Your child will need to have regular
special low-protein flours, pastas, and
blood tests to measure ammonia and
rice that are made especially for people
amino acid levels. Your childs diet and
with amino acid disorders.
medication may need to be adjusted
based on blood test results.

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4. Call your doctor at the start of any Even with treatment, some children
illness: still have effects from high blood levels
Illness or infection can sometimes lead of arginine and ammonia. This can
to high arginine and ammonia levels. In result permanent learning problems,
order to prevent problems, call your mental retardation or spasticity.
doctor right away when your child has
What causes the arginase enzyme to
any of the following:
be absent or not working correctly?
loss of appetite
Genes tell the body to make various
low energy or excessive sleepiness
enzymes. People with arginase
vomiting
deficiency have a pair of genes that do
fever
not work correctly. Because of the
infection or illness
changes in this pair of genes, the
behavior or personality changes
arginase enzyme either does not work
difficulty walking or balance
properly or is not made at all.
problems

How is arginase deficiency


Children with symptoms of high blood
inherited?
ammonia may need to be treated in a
hospital. Ask your metabolic doctor if This condition is inherited in an
you should carry a special travel letter autosomal recessive manner. It affects
with medical instructions for your
both boys and girls equally.
childs care.
Everyone has a pair of genes that make
What happens when arginase the arginase enzyme. In children with
deficiency is treated?
arginase deficiency, neither of these
genes works correctly. These children
With prompt and lifelong treatment,
inherit one non-working gene for the
children with arginase deficiency may
condition from each parent.
be able to live healthy lives with typical
growth and learning.

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Parents of children with arginase there is a 25% chance for the child to
deficiency rarely have the condition have two working genes.
themselves. Instead, each parent has a
Genetic counseling is available to
single non-working gene for arginase
families who have children with this
deficiency. They are called carriers.
condition. Genetic counselors can
Carriers do not have the condition
answer your questions about how
because the other gene of this pair is
arginase deficiency is inherited,
choices during future pregnancies, and
how to test other family members. Ask
your doctor about a referral to a genetic
counselor.

Is genetic testing available?


Genetic testing for arginase deficiency
is available. Genetic testing, also called
DNAtesting, looks for changes in the
pair of genes that causes the condition.
Talk with your genetic counselor or
metabolic doctor about whether DNA
testing is possible for your family.

DNA testing is not necessary to


diagnose your child. It can be helpful
working correctly.
for carrier testing or prenatal diagnosis,
When both parents are carriers, there discussed below.
is a 25% chance in each pregnancy for
What other testing is available?
the child to have arginase deficiency.
There is a 50% chance for the child to Special blood and urine tests can be
be a carrier, just like the parents. And, done to confirm arginase deficiency.

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Talk to your metabolic doctor or Having arginase deficiency


genetic counselor if you have questions If they are healthy and growing
about diagnostic testing. normally, older brothers and sisters of
baby with arginase deficiency are at
Can you test during pregnancy?
low risk of having the condition.
However, finding out whether other
If both gene changes have been found
children in the family have the
in your child with arginase deficiency,
condition may be important because
DNA testing can be done during future
early treatment can prevent serious
pregnancies. The sample needed for
health problems. Ask your metabolic
DNA testing is obtained by either CVS
doctor whether your other children
or amniocentesis.
should be tested.
If DNA testing is not possible, an
Arginase deficiency carriers:
enzyme test may be done using a blood
Brothers and sisters who do not have
sample from the fetus. The sample
arginase deficiency still have a chance
needed is obtained by a procedure
to be carriers like their parents. Except
called fetal blood sampling.
in special cases, carrier testing should
Parents may either choose to have only be done in people over 18 years of
testing during pregnancy or wait until age.
birth to have the baby tested. A genetic
Each of the parents brothers and
counselor can talk to you about your
sisters has a 50% chance to be a
choices and answer questions about
carrier. It is important for other family
prenatal testing or testing your baby
members to be told that they could be
after birth.
carriers. There is a small chance they
Can other members of the family are also at risk to have children with
have arginase deficiency or be arginase deficiency.
carriers?
Some states do not offer newborn
screening for arginase deficiency.

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However, expanded newborn screening Arginase protein estimation in


through private labs is available for red cell hemolysate by
babies born in states that do not screen Western blot test.
for this condition.
Center for testing

When both parents are carriers, PreventiNe Lifecare Pvt. Ltd.

newborn screening results are not RPT House, Plot No. 6, Sector 24,

sufficient to rule out the condition in a Turbhe, Navi Mumbai 400705

newborn baby. In this case, special Ph: 022-61980000/11

diagnostic testing should be done in


addition to newborn screening. Medical Genetics Laboratories
Baylor College of Medicine
Can other family members be tested? 2450 Holcombe, Grand Blvd. -
Receiving Dock
Diagnostic testing: Brothers and
Houston, TX 77021-2024
sisters of a child with arginase
Ph: 713-798-6555
deficiency can be tested using blood,
E-mail: genetictest@bcm.edu
urine or skin samples.

What is the cost of the confirmatory


Carrier testing: Carrier testing may be
test?
available. Your metabolic doctor or
genetic counselor can answer your 350 (+ 100 for fibroblast culturing).
questions about carrier testing.
How many people have arginase
Where can Confirmatory testing done deficiency?
for this condition?
About one in every 300,000 babies in
The confirmatory test for the the United States is born with this
diagnosis of the disorder is done by condition.
Estimation of Blood Arginine
Does arginase deficiency happen
levels.
more often in a certain ethnic group?

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No, it does not happen more often in


any specific race, ethnic group,
geographical area or country.

Does arginase deficiency go by any


other names?

Arginase deficiency is sometimes also


called:

Argininemia
ARG1 deficiency
Hyperargininemia

Where can I find more information?

National Urea Cycle Disorders


Foundation
http://www.nucdf.org/

Children Living with Inherited


Metabolic Diseases (CLIMB)
http://www.climb.org.uk

Genetic Alliance
http://www.geneticalliance.org

Urea Cycle Disorders Consortium


Registry
http://rarediseasesnetwork.epi.usf.edu/
ucdc/

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A
Where can Confirmatory Testing
rgininosuccinic

be done for this condition?


acid lyase What is the cost of the
confirmatory test?
deficiency How many people have ASAL

Disorder name: Argininosuccinic deficiency?

acid lyase deficiency Does ASAL deficiency happen

Acronym: ASAL deficiency more often in a certain ethnic


group?
What is ASAL deficiency? Does ASAL deficiency go by any
What causes ASAL deficiency? other names?
If ASAL deficiency is not treated, Where can I find more
what problems occur? information?
What is the treatment for ASAL
deficiency? This fact sheet contains general

What happens when ASAL information about ASAL deficiency.

deficiency is treated? Every child is different and some of

How is ASAL deficiency these facts may not apply to your child

inherited? specifically. Certain treatments may be

What causes the ASAL enzyme to recommended for some children but

be absent or not working not others. All children with this

correctly? condition should be followed by a

Is genetic testing available? metabolic doctor in addition to their

What other testing is available? primary doctor.

Can you test during pregnancy?


What is ASAL deficiency?
Can other members of the family
have ASAL deficiency or be ASAL stands for argininosuccinic acid

carriers? lyase. ASAL deficiency is one type of

Can other family members be amino acid disorders. People with this

tested? condition cannot remove ammonia

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Amino Acid Disorder: its building blocks, amino acids, are


broken down for use by the body.
Amino acid disorders (AAs) are a group
of rare inherited conditions. They are What causes ASAL deficiency?
caused by enzymes that do not work
ASAL deficiency is one of a small
properly.
number of conditions called urea cycle

Protein is made up of smaller building disorders (UCD).

blocks called amino acids. A number of


It occurs when an enzyme called
different enzymes are needed to process
argininosuccinic acid lyase (ASAL),
these amino acids for use by the body.
is either missing or not working
Because of missing or non-working
properly. This enzymes job is to help
enzymes, people with amino acid
remove ammonia from the body.
disorders cannot process certain amino
acids. These amino acids, along with When the ASAL enzyme is not
other toxic substances, then build up in working, ammonia and other harmful
the body and cause problems. substances build up in the blood and
cause brain damage. If not treated,
The symptoms and treatment vary
excess ammonia can cause death.
between different amino acid disorders.
They can also vary from person to person
with the same amino acid disorder. See
the fact sheets for each specific amino
acid disorder.

Amino acid disorders are inherited in an


autosomal recessive manner and affect
both males and females.

from the body. Ammonia is a harmful


substance. It is made when protein and

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the most common form, the symptoms


start shortly after birth. There is also a
milder form in which symptoms start in
late infancy or early childhood.

ASAL deficiency in newborns


Infants are healthy at birth but quickly
develop symptoms. Within a few days
of life, babies have high levels of
ammonia in their blood. Some of the
first symptoms of high blood ammonia
are:

poor appetite
excess sleepiness or lack of
energy
If ASAL deficiency is not treated, irritability
what problems occur?
vomiting
Normally, the body changes ammonia
into a substance called urea. Urea is If not treated, high ammonia levels can

then safely removed in the urine. If cause:

ammonia is not changed to urea, it muscle weakness

begins to build up in the blood and can decreased or increased muscle

be very harmful. If ammonia levels tone

remain high for too long, severe brain breathing problems

damage can occur. problems staying warm


seizures
The symptoms and the age they start swelling of the brain
vary from person to person. There are coma, and sometimes death
two main forms of ASAL deficiency. In

29 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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BABYSHIELD TMS FACT SHEET

Other effects of ASAL deficiency can Episodes of high blood ammonia often
include: happen:
poor growth after long periods of going
enlarged liver without food
delays in learning or mental during illness or infection
retardation after high-protein meals

Without treatment, many babies die In children, some of the first symptoms
within the first few weeks of life.
of high blood ammonia are:
ASAL deficiency in childhood poor appetite
In this milder form, symptoms start intense headache
later in infancy or childhood. Some vomiting
common symptoms in children who are extreme sleepiness or lack of
not treated are: energy
slurred speech
poor growth
poor coordination and balance
dry, brittle hair
problems
hyperactivity
behavior problems If not treated, children with high blood
learning disabilities or mental ammonia levels can develop:
retardation breathing problems
avoidance of meat and other swelling of the brain
high protein foods seizures
enlarged liver coma, sometimes leading to
small head size death
episodes of excess ammonia in
Some people have very mild symptoms
the blood
and are only found to be affected after a
brother or sister is diagnosed.

What is the treatment for ASAL


deficiency?

30 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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Your babys primary doctor will work meat and poultry


with a metabolic doctor and a dietician fish
to care for your child. eggs
dried beans and legumes
Prompt treatment is needed to prevent
nuts and peanut butter
the build-up of ammonia. You should
start treatment as soon as you know Eating foods high in protein can cause
your child has this condition. ammonia to build up in the blood,
resulting in severe illness. Many
The following are treatments often
vegetables and fruits have only small
recommended for babies and children
amounts of protein and can be eaten in
with ASAL deficiency:
carefully measured amounts.

1. Low-protein diet and/or special


Do not remove all protein from the diet.
medical foods and formula
Your child still needs a certain amount
Most children need to eat a diet made
of protein for normal growth and
up of very low-protein foods, special
development. Your dietician will help
medical foods, and sometimes a special
you create the best food plan for your
formula. Your dietician will create a
child.
food plan that contains the right
amount of protein, nutrients, and Medical foods and formula
energy to keep your child healthy. The
There are medical foods such as
food plan should be continued
special low-protein flours, pastas, and
throughout your childs life.
rice made especially for people with
Low-protein diet amino acid disorders.
The most effective treatment is a low-
Your baby may be given a special
protein diet. Foods that need to be
formula that contains the correct
avoided or strictly limited include:
amount of nutrients and amino acids.
milk, cheese and other dairy
Your metabolic doctor and dietician
products

31 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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will decide whether your child needs During episodes of high blood
this formula. Some states offer help ammonia, children need to be treated in
with payment, or require private the hospital. Medications to remove
insurance to pay for the formula and ammonia are often given by IV.
other special medical foods. Sometimes dialysis is needed to
Your childs exact food plan will remove ammonia from the blood.
depend on many things such as his or
3. Blood tests
her age, weight, and general health.
Your child will have regular blood tests
Your dietician will fine-tune your
to measure amino acid and ammonia
childs diet over time. Any diet
levels. Your childs diet and medication
changes should be made under the
may need to be adjusted based on
guidance of a dietician familiar with
blood test results.
ASAL deficiency.

4. Call your doctor at the start of any


2. Medication
illness:
Most children with ASAL deficiency
are given arginine supplements by For some babies and children, even
mouth. Arginine helps the body remove
minor illness can lead to build up of
ammonia from the blood. Your doctor
ammonia. In order to prevent problems,
will tell you whether your child needs call your doctor right away when your
these supplements and how much to child has any of the following:
take.
loss of appetite
There are other medications that can
low energy or extreme
help prevent high ammonia levels. sleepiness
These can either be taken by mouth or vomiting
by tube feedings. Your metabolic
fever
doctor will decide whether your child
infection or illness
needs this type of medication.
behavior or personality changes

32 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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difficulty walking or balance With prompt and lifelong treatment,


problems children with ASAL deficiency may be
able to live healthy lives with typical
Symptoms of high ammonia often need
growth and learning. Early treatment
to be treated in the hospital. Ask your
can help prevent high ammonia levels.
metabolic doctor if you should carry a
This lessens the risk for brain damage
special travel letter with medical
and mental retardation.
instructions for your childs care.
Even with treatment, some children
5. Liver transplantation
still have episodes of high ammonia.
Liver transplant surgery has been tried
This can result in brain damage and
in some children with ASAL who do
can cause lifelong learning problems,
not respond to dietary treatment. Liver
mental retardation, or spasticity.
transplant in children with ASAL
deficiency does not cure the underlying What causes the ASAL enzyme to be
disease and is only done when absent or not working correctly?
necessary. Genes tell the body to make various
enzymes. People with ASAL deficiency
This major surgical procedure is
have a pair of genes that do not work
associated with risks, and individuals
correctly. Because of the changes in
who have had a liver transplant must
this pair of genes, the ASAL enzyme
take medication for the rest of their
either does not work properly or is not
lives to prevent their body from
made at all.
rejecting the donor liver. Many factors
must be considered before surgery and How is ASAL deficiency inherited?
this option should be discussed This condition is inherited in an
thoroughly with your childs doctors. autosomal recessive manner. It affects
both boys and girls equally.
What happens when ASAL deficiency
is treated? Everyone has a pair of genes that make
the ASAL enzyme. In children with

33 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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ASAL deficiency, neither of these When both parents are carriers, there
genes works correctly. These children is a 25% chance in each pregnancy for
inherit one non-working gene for the the child to have ASAL deficiency.
condition from each parent. There is a 50% chance for the child to
be a carrier, just like the parents. And,
Parents of children with ASAL
there is a 25% chance for the child to
deficiency rarely have the condition
have two working genes.
themselves. Instead, each parent has a
Genetic counseling is available to
families who have children with ASAL
deficiency. Genetic counselors can
answer your questions about how the
condition is inherited, choices during
future pregnancies, and how to test
other family members. Ask your doctor
about a referral to a genetic counselor.

Is genetic testing available?


Genetic testing for ASAL deficiency is
available. Genetic testing, also called
DNA testing, looks for changes in the
pair of genes that cause the condition.
Ask your metabolic doctor or genetic
counselor whether DNA testing is
available to your family.

single non-working gene for ASAL DNA testing is not necessary to


deficiency. They are called carriers. diagnose your child. It can be helpful
Carriers do not have the condition for carrier testing or prenatal diagnosis,
because the other gene of this pair is discussed below.
working correctly.

34 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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What other testing is available? Having ASAL deficiency


Special tests on blood, urine or skin The brothers and sisters of a baby with
samples can be done to confirm ASAL ASAL deficiency have a small chance
deficiency. Talk to your metabolic of being affected, even if they havent
doctor or genetic counselor if you have had symptoms. Finding out if other
questions about this type of testing. children in the family have this
condition is important because early
Can you test during pregnancy?
treatment can prevent serious health
If both gene changes have been found
problems. Talk to your metabolic
in your child with ASAL deficiency,
doctor or genetic counselor about
DNA testing can be done during future
testing your other children.
pregnancies. The sample needed for
this test is obtained by either CVS or ASAL deficiency carriers
amniocentesis. Brothers and sisters who do not have
the condition still have a chance to be
If DNA testing would not be helpful, an
carriers like their parents. Except in
enzyme test can be done on cells from
special cases, carrier testing should
the fetus. Again, the sample needed for
only be done in people over 18 years of
this test is obtained by either CVS or
age.
amniocentesis.
Each of the parents brothers and
Parents may choose to have testing
sisters has a 50% chance to be a
during pregnancy or wait until birth to
carrier. It is important for other family
have the baby tested. A genetic
members to be told that they could be
counselor can talk to you about your
carriers. There is a chance they are
choices and answer questions about
also at risk to have children with ASAL
prenatal testing or testing your baby
deficiency.
after birth.
All states offer newborn screening for
Can other members of the family
ASAL. However, when both parents are
have ASAL deficiency or be carriers?
carriers, newborn screening results are

35 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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not sufficient to rule out the condition (GC/MS) using urine sample or by
in a newborn baby. In this case, special Argininosuccinate lyase enzyme
diagnostic testing should be done in assay done on cultured fibroblasts for
addition to newborn screening. confirmatory test.

Can other family members be tested?


Center

Diagnostic testing Laboratory Genetic Metabolic


Diseases
Brothers and sisters of a child with
Academic Medical Center
ASAL deficiency can be tested using
Laboratory Genetic Metabolic
blood, urine or skin samples.
Diseases (F0-132)
Carrier testing Meibergdreef 9
If both gene changes have been found 1105 AZ Amsterdam
in your child, other family members The Netherlands
can have DNA testing to see if they are Ph - +31 20 5662026 / 5393
carriers.
What is the cost of the confirmatory

If the gene changes cannot be found, test?

DNA testing would not be helpful for 350 (+ 100 for fibroblast culturing).

carrier testing. However, other methods


of carrier testing may be available. How many people have ASAL

Your metabolic doctor or genetic deficiency?

counselor can answer your questions This is a rare condition. About one in
every 70,000 babies in the United
about carrier testing.
States is born with ASAL deficiency.
Where can Confirmatory Testing be
done for this condition? Does ASAL deficiency happen more
frequently in a certain ethnic group?
The confirmatory test for the
diagnosis is done by Gas
Chromatography Mass Spectrometry

36 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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BABYSHIELD TMS FACT SHEET

ASAL deficiency does not happen more Urea Cycle Disorders Consortium
Registry
often in any specific race, ethnic group,
http://rarediseasesnetwork.epi.usf.edu/
geographical area or country. ucdc/

Does ASAL deficiency go by any


other names?

ASAL deficiency is sometimes also


called:
Argininosuccinase deficiency
Argininosuccinic aciduria
Argininosuccinic acidemia
Argininosuccinic acid lyase
deficiency
ASL deficiency
ASA
Arginine succinate lyase
deficiency

Where can I find more information?


National Urea Cycle Disorders
Foundation
http://www.nucdf.org/

Children Living with Inherited


Metabolic Diseases (CLIMB)
http://www.climb.org.uk

Genetic Alliance
http://www.geneticalliance.org

37 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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C
How many people have
itrullinemia

citrullinemia?
Does citrullinemia happen more
often in a certain ethnic group?
Disorder name: Citrullinemia Does citrullinemia go by any other
Acronym: ASAS names?
Where can I find more
What is citrullinemia?
information?
What causes citrullinemia?
If citrullinemia is not treated, This fact sheet contains general
what problems occur? information about citrullinemia. Every
What is the treatment for child is different and some of these
citrullinemia? facts may not apply to your child
What happens when citrullinemia specifically. Certain treatments may be
is treated? recommended for some children but
What causes the ASAS enzyme to not others. All children with this
be absent or not working condition should be followed by a
correctly? metabolic doctor in addition to their
How is citrullinemia inherited? primary doctor.
Is genetic testing available?
What is citrullinemia?
What other testing is available?
Citrullinemia is one type of amino acid
Can you test during pregnancy?
disorder. People with this condition
Can other members of the family
cannot remove ammonia from the
have citrullinemia or be carriers?
body. Ammonia is a harmful
Can other family members be
substance. It is made when protein and
tested?
its building blocks, amino acids, are
Where can Confirmatory Testing
broken down for use by the body.
be done for this condition?
What is the cost of the
confirmatory test?

38 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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What causes citrullinemia? enzyme called Argininosuccinate


This is one of a small number of synthetase (ASAS), is either missing
conditions called urea cycle or not working properly. This enzymes
disorders (UCD). It occurs when an job is to help break down certain amino
acids and to remove ammonia from the

Amino Acid Disorders: body.

Amino acid disorders (AAs) are a group When ASAS is not working, an amino

of rare inherited conditions. They are acid called citrulline builds up in the

caused by enzymes that do not work blood. Ammonia and other harmful

properly. substances also build up. This causes


brain damage. If not treated, excess
Protein is made up of smaller building ammonia in the blood can cause death.
blocks called amino acids. A number of
different enzymes are needed to process
these amino acids for use by the body.
Because of missing or non-working
enzymes, people with amino acid
disorders cannot process certain amino
acids. These amino acids, along with
other toxic substances, then build up in
the body and cause problems.

The symptoms and treatment vary


between different amino acid disorders.
They can also vary from person to person
with the same amino acid disorder. See
the fact sheets for each specific amino
acid disorder.

Amino acid disorders are inherited in an


autosomal recessive manner and affect
NEWBORN SCREENING- SCREEN EARLY TREAT EARLY
both39
males and females.
Unauthorised reproduction of this article is prohibited
BABYSHIELD TMS FACT SHEET

The symptoms, and the age they start,


vary from person to person. There are
two main forms of this condition. The
most common is called classic. It
usually starts in infancy. There are also
milder forms that start later in infancy
or childhood. There is also a rare adult
form more common in people from
Japan. Some women only have
symptoms during or after pregnancy.

Classic citrullinemia
Infants seem healthy at birth but
quickly develop symptoms. Within a
few days of life, babies will have high
levels of ammonia in their blood. Some
of the first symptoms of high blood
ammonia are:

poor appetite
If citrullinemia is not treated, what
extreme sleepiness or lack of
problems occur?
energy
Normally, the body changes ammonia
irritability
into a substance called urea. Urea is
vomiting
then safely removed in the urine. If
ammonia is not changed to urea, high
If not treated, high ammonia levels
levels build up in the blood. This can
cause:
be very harmful. If ammonia levels stay muscle weakness
high for too long, severe brain damage
decreased or increased muscle
can occur. tone
breathing problems

40 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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BABYSHIELD TMS FACT SHEET

problems staying warm episodes of high levels of


seizures ammonia in the blood
swelling of the brain liver failure
coma, and sometimes death
Episodes of high blood ammonia often
Other effects of citrullinemia can happen:
include: after going without food for long
poor growth periods of time
enlarged liver during illness or infection
learning delays or mental after high-protein meals
retardation
Some of the first symptoms of high
Without treatment, most babies die blood ammonia in children are:
within the first few weeks of life. poor appetite
severe headache
Milder forms
vomiting
In the milder forms, symptoms start
extreme sleepiness or lack of
later in infancy or childhood.
energy
Symptoms in untreated children can
slurred speech
include:
poor coordination or balance
poor growth
problems
dry, brittle hair
hyperactivity If not treated, children with high blood
behavior problems ammonia levels may develop:
learning problems or mental breathing problems
retardation swelling of the brain
avoidance of meat and other seizures
high-protein foods coma, sometimes leading to
spasticity death
Stroke

41 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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A rare form of citrullinemia occurs 1. Low-protein diet and/or special


during and after pregnancy. Women medical foods and formula
may experience: Most children need to eat a diet made
vomiting up of very low-protein foods, special
lethargy medical foods, and, sometimes, a
seizures special formula. Your dietician will
confusion and hallucinations create a food plan that contains the
changes in behavior including right amount of protein, nutrients, and
manic episodes and psychosis energy to keep your child healthy. A
swelling of the brain special food plan should be continued
throughout your childs life.
Some people have very mild or no
symptoms and are only found to be Low-protein diet
affected after a brother or sister is The most effective treatment for
diagnosed. citrullinemia is a low-protein diet.
Foods that need to be avoided or
What is the treatment for
strictly limited include:
citrullinemia?
Your babys primary doctor will work milk, cheese, and other dairy
with a metabolic doctor and a dietician products
to care for your child. meat and poultry
fish
Prompt treatment is needed to prevent
eggs
the build-up of ammonia. You should
dried beans and legumes
start treatment as soon as you know
nuts and peanut butter
your child has the condition.
Eating foods high in protein can cause
The following are treatments often
ammonia to build up, causing severe
recommended for babies and children
illness. Many vegetables and fruits
with citrullinemia:
have only small amounts of protein and
can be eaten in carefully measured

42 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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amounts. 2. Medication
Do not remove all protein from the diet. There are certain medications that can
Your child still needs a certain amount help the body get rid of ammonia.
of protein for normal growth and These are taken by mouth or by tube
development. Any changes in the diet feeding to prevent high ammonia
should be made under the guidance of levels. Your doctor will decide whether
a dietician. your child needs these medications,
which ones, and how much to use.
Medical foods and formula
There are medical foods such as During episodes of high ammonia,
special low-protein flours, pastas, and children need to be treated in the
rice that are made especially for people hospital. Medications to remove
with amino acid disorders. ammonia are often given by IV.
Dialysis is sometimes needed to
Your baby may need to drink a special
remove ammonia from the blood.
medical formula that contains the
correct amount of amino acids and An amino acid called arginine is often
nutrients. Your metabolic doctor and given by mouth to help prevent
dietician will decide whether your child ammonia build-up. Your doctor will tell
needs this treatment. Some states offer you whether your child needs arginine
help with payment, or require private and how much to use. Do not use any
insurance to pay for the formula and supplements or medications without
other special medical foods. checking with your doctor.

Your childs exact food plan will 3. Blood tests


depend on many things such as his or Your child will have regular blood tests
her age, weight, and general health. to measure ammonia and amino acid
Your dietician will fine-tune your levels. Your childs diet and medication
childs diet over time. Any diet may need to be adjusted based on
changes should be made under the blood test results.
guidance of a dietician.

43 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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4. Call your doctor at the start of any The ASAS enzyme that causes
illness: citrullinemia is located in the liver.
For some babies and children with Because of this, some children with
citrullinemia, even minor illness can citrullinemia have had liver
cause high ammonia levels. In order to transplantation surgery (removal of
prevent problems, call your doctor right their liver and replacement with a
away when your child has any of the donor liver) to treat their citrullinemia
following: symptoms.

loss of appetite This major surgical procedure is


low energy or extreme associated with risks, and individuals
sleepiness who have had a liver transplant must
vomiting take medication for the rest of their
fever lives to prevent their body from
infection or illness rejecting the donor liver. However,
behavior or personality changes successful liver transplantation has
difficulty walking or balance been reported to improve quality of life
problems and prolong survival in some cases.

Symptoms of high ammonia often need Many factors must be considered


to be treated in the hospital. Ask your before surgery and this option should
metabolic doctor if you should carry a be discussed very thoroughly with your
special travel letter with medical childs physicians.
instructions for your childs care.
What happens when citrullinemia is
5. Liver transplantation treated?
Liver transplant surgery is an optional
treatment for people with citrullinemia.

44 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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With prompt and lifelong treatment, one non-working gene for the condition
children with citrullinemia can often
live healthy lives with typical growth
and learning. Early treatment can help
prevent high ammonia levels.

Even with treatment, some children


still have episodes of high ammonia.
This can result in brain damage. This
can cause lifelong learning problems,
mental retardation or spasticity.

What causes the ASAS enzyme to be


absent or not working correctly?
Genes tell the body to make various
enzymes. People with citrullinemia
have a pair of genes that do not work
correctly. Because of the changes in
this pair of genes, the ASAS enzyme
either does not work properly or is not
from each parent.
made at all.

Parents of a child with citrullinemia


How is citrullinemia inherited?
rarely have the condition themselves.
This condition is inherited in an
Instead, each parent has a single non-
autosomal recessive manner. It affects
working gene for citrullinemia. They
both boys and girls equally.
are called carriers. Carriers do not have
Everyone has a pair of genes that make the condition because the other gene of
the ASAS enzyme. In children with this pair is working correctly.
citrullinemia, neither of these genes
works correctly. These children inherit

45 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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When both parents are carriers, there citrullinemia. Talk to your metabolic
is a 25% chance in each pregnancy for doctor or genetic counselor if you have
the child to have citrullinemia. There is questions about this type of testing.
a 50% chance for the child to be a
carrier, just like the parents. And, there
is a 25% chance for the child to have
two working genes.
Can you test during pregnancy?
Genetic counseling is available to If both gene changes have been found
families who have children with this in your child, DNA testing can be done
condition. Genetic counselors can during future pregnancies. The sample
answer your questions about how it is needed for this test is obtained by
inherited, choices during future either CVS or amniocentesis.
pregnancies, and how to test other
family members. Ask your doctor about If DNA testing would not be helpful, an

a referral to a genetic counselor. enzyme test can be done on cells from


the fetus. Again, the sample needed for
Is genetic testing available? this test is obtained by either CVS or
Genetic testing can be done on a blood amniocentesis.
sample. Genetic testing, also called
DNA testing, looks for changes in the Although prenatal testing is possible,

pair of genes that cause the condition. many parents choose to wait until birth
to have the baby tested. A genetic
DNA testing is not necessary to counselor can talk to you about your
diagnose your child. It can be helpful choices and answer questions about
for carrier or prenatal testing, prenatal testing or testing after birth.
discussed below.
Can other members of the family
What other testing is available? have citrullinemia or be carriers?
Special tests on blood, urine or skin
samples can be done to confirm Having citrullinemia

46 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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The brothers and sisters of a baby with rule out the condition in a newborn
citrullinemia have a chance of being baby. In this case, special diagnostic
affected, even if they havent had testing should be done in addition to
symptoms. Finding out whether other newborn screening.
children in the family have the
Can other family members be tested?
condition is important because early
treatment can prevent serious health Diagnostic testing
problems. Talk to your metabolic
Brothers and sisters of a child with
doctor or genetic counselor about
citrullinemia can be tested using blood,
testing your other children.
urine, or skin samples.

Citrullinemia carriers
Brothers and sisters who do not have
citrullinemia still have a chance to be
carriers like their parents. Except in
Carrier testing
special cases, carrier testing should
only be done in people over 18 years of If both gene changes have been found
age. in your child, other family members
can have genetic testing to see if they
Each of the parents brothers and
are carriers.
sisters has a 50% chance to be a
carrier. It is important for other family If DNA testing would not be helpful,
members to be told that they could be other methods of carrier testing may be
carriers. There is a chance they are available. Your metabolic doctor or
also at risk to have children with genetic counselor can answer your
citrullinemia. questions about carrier testing.

All states offer newborn screening for Where can Confirmatory Testing be
citrullinemia. However, when both done for this condition?
parents are carriers, newborn
screening results are not sufficient to The confirmatory test for the

47 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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diagnosis of Citrullinemia type I is Citrullinemia is sometimes also called:


done by Liquid Chromatography
Citrullinemia, type 1 (classic
Mass Spectrometry (LC/MS) using
form)
urine sample.
Argininiosuccinate synthetase
deficiency
Center
Arginininosuccinic acid
PreventiNe Lifecare Pvt. Ltd.
synthetase deficiency
RPT House, Plot No. 6, Sector 24,
AS deficiency
Turbhe, Navi Mumbai 400705
ASS deficiency
Ph:
Citrullinuria
022-
CTLN1
61980
000/1 The adult-onset form of citrullinemia is
1 also called:

Late-onset citrullinemia

How many people have


A disorder which was originally
citrullinemia? thought to be related to Citrullinemia
but is now known to be a separate
This is a rare condition. About one in
disorder is called:
every 57,000 babies in the United
States is born with citrullinemia. Citrullinemia, Type II Or Citrin
Deficiency
Does citrullinemia happen more
frequently in a certain ethnic group? Where can I find more information?

The classic form of citrullinemia occurs National Urea Cycle Disorders


in all ethnic groups around the world.
Foundation
http://www.nucdf.org/
Does citrullinemia go by any other
names?

48 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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Children Living with Inherited


Metabolic Diseases (CLIMB)
http://www.climb.org.uk

Genetic Alliance
http://www.geneticalliance.org

Urea Cycle Disorders Consortium


http://rarediseasesnetwork.epi.usf.edu/
ucdc/

49 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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H
What is the cost of the
omocystinuria

confirmatory test?
How many people have
homocystinuria?
Disorder name: Homocystinuria Does homocystinuria happen
more often in a certain ethnic
What is homocystinuria?
group?
What causes homocystinuria?
Does homocystinuria go by any
If homocystinuria is not treated,
other names?
what problems occur?
Where can I find more
What is the treatment for
information?
homocystinuria?
What happens when This fact sheet contains general
homocystinuria is treated? information about homocystinuria.
What causes the CBS enzyme to Every child is different and some of
be absent or not working these facts may not apply to your child
correctly? specifically. Certain treatments may be
How is homocystinuria inherited? recommended for some children but
Is genetic testing available? not others. Children with this condition
What other testing is available? should be followed by a metabolic
Can you test during pregnancy? doctor in addition to their primary care
Can other members of the family provider.
have homocystinuria or be
carriers? What is homocystinuria?

Can other family members be It is one type of amino acid disorder.

tested? People with this condition have

Where can Confirmatory Testing problems breaking down an amino acid

be done for this condition? called methionine from the food they
eat.

50 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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What causes homocystinuria? Special enzymes then make changes to


In order for the body to use protein the amino acids so the body can use
from the food we eat, it is broken down them.
into smaller parts called amino acids.
This condition occurs when an enzyme
called cystathionine beta-synthase
Amino Acid Disorders:
(CBS) is either missing or not working

Amino acid disorders (AAs) are a group properly. This enzymes job is to break

of rare inherited conditions. They are


caused by enzymes that do not work
properly.

Protein is made up of smaller building


blocks called amino acids. A number of
different enzymes are needed to process
these amino acids for use by the body.
Because of missing or non-working
enzymes, people with amino acid
disorders cannot process certain amino
acids. These amino acids, along with
other toxic substances, then build up in
the body and cause problems.

The symptoms and treatment vary


between different amino acid disorders.
They can also vary from person to
person with the same amino acid
disorder. See the fact sheets for each down methionine. When the CBS

specific amino acid disorder. enzyme is not working correctly,


methionine and another amino acid,
Amino acid disorders are inherited in an
autosomal recessive manner and affect
NEWBORN SCREENING- SCREEN EARLY TREAT EARLY
both51
males and females.
Unauthorised reproduction of this article is prohibited
BABYSHIELD TMS FACT SHEET

homocystine, build up in the blood and serious learning disabilities or


cause problems. mental retardation

If homocystinuria is not treated, what Eyes


problems occur? Children usually start to develop severe
Babies look healthy and normal at nearsightedness after one year of age.
birth. Over time, if the condition is not If this is not treated, the lens of the eye
treated, it can cause growth and can become loose and move out of
learning delays. It can also affect the place. This is called lens dislocation.
eyes, bones, heart, and blood vessels. This often happens between two and
eight years of age. Glaucoma, a
There are two types of homocystinuria.
condition caused by increased eye
The milder form can be treated with
pressure, can happen over time if the
vitamin B6 supplements. The other
lens dislocation is not treated.
type does not respond to vitamin B6.
Untreated glaucoma can cause
Symptoms of both types vary widely
blindness.
from person to person.
Bones and skeleton
Growth, learning and behavior
Teens and adults are often very tall and
Delays in growth and learning are often
slender. They may have very long
noticed between the ages of one and
arms, legs, and fingers. By the teen-age
three. Common effects in untreated
years, about half have thinning of the
children include:
bones, called osteoporosis.

poor growth
Muscle weakness, especially in the
problems gaining weight
legs, is a problem for some children.
delays in crawling, walking, and
talking Heart and blood vessels
behavior and emotional If not treated, homocystinuria can
problems cause blot clots resulting in heart
disease or stroke. In fact, stroke and

52 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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heart disease are the main causes of The following are treatments often
early death in people with untreated recommended for children with
homocystinuria. homocystinuria:

Other 1. Low-methionine diet:


Children who are not treated often have The special diet is made up of foods
pale hair and skin. Some will have that are very low in methionine. This
episodes of pancreatitis that causes means your child must not have cows
severe pain, and some may have milk, regular formula, meat, fish,
seizures. cheese, or eggs. Regular flour, dried
beans, nuts, and peanut butter also
What is the treatment for
contain methionine and must be
homocystinuria?
avoided or strictly limited.

Your babys primary doctor will work


Many vegetables and fruits have only
with a metabolic doctor and a dietician
small amounts of methionine and can
to care for your child.
be eaten in carefully measured
amounts. There are other medical
Prompt treatment is needed to prevent
foods such as special low-protein
mental retardation and other serious
or low-methionine flours, breads, and
health problems. Most children need to
eat a special diet low in methionine, pastas that are made especially for
people with homocystinuria.
drink a special formula, and take
supplements every day. You should
Your metabolic doctor and dietician
start the treatment as soon as you
will decide on the best food plan for
know your child has this condition.
your child. Your childs diet will
Lifelong treatment is usually needed to
depend on many things such as his or
prevent or control the symptoms.
her age, weight, and blood test results.
Your dietician will fine-tune your
childs diet over time. The diet is
usually needed throughout life.

53 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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2. Medical Foods and Formula Ask your metabolic doctor whether


In addition to a low-methionine diet, your child would benefit from vitamin
some children are given a special B6 supplements. Your doctor can do
medical formula as a substitute for special tests to figure out whether your
milk. This formula will give your child child will respond to vitamin B6.
the correct amount of nutrients and
Betaine
protein while helping to keep his or her
Betaine is a vitamin-like substance
methionine and homocystine levels
found in grains and other foods. It can
within a safe range. Your metabolic
also be bought in pill form as a
doctor and dietician will tell you what
supplement. Betaine can help lower the
type of formula is best for your child
amount of homocystine in the blood,
and how much to use.
and may be especially helpful for
Some states offer help with payment, or children who do not respond to vitamin
require private insurance coverage for B6. It may also lessen the risk of blood
formula and other special medical clots.
foods.
Your metabolic doctor will decide
3. Supplements whether your child needs betaine.
Unless you are advised otherwise, use
Vitamin B6
only betaine prescribed by your doctor.
Some children are helped by vitamin
B6 supplements. In children who
benefit from this treatment, the
Vitamin B12
supplements help prevent mental
Some people with homocystinuria have
retardation and behavior problems.
low levels of vitamin B12 in their blood.
Vitamin B6 may also reduce the risk for
They may need to have vitamin B12
blood clotting and eye and bone
injections. Ask your doctor whether
problems.
your child needs extra vitamin B12.

54 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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Folic Acid 5. Pregnancy


Some people have low levels of folic Pregnancy increases the risk for blood
acid, a type of B vitamin, in their blood. clots, stroke, and heart disease in
They may need to take folic acid women with homocystinuria. Women
supplements by mouth. This vitamin are often given blood thinning
can help lower the level of homocystine medication during the last few months
in the blood. Ask your doctor whether of pregnancy until about 6 weeks after
your child needs folic acid delivery.
supplements.
The usual treatments for
L-cystine homocystinuria should be continued
People with homocystinuria may have during pregnancy. In addition to blood
low levels of another amino acid called clots, untreated women are at higher
L-cystine. L-cystine may already be risk for miscarriage and stillbirth.
part of the special medical formula. If
What happens when homocystinuria
not, it can be taken by mouth as a
is treated?
supplement. Unless you are advised
With lifelong treatment, many children
otherwise, use only L-cystine
have normal growth and intelligence.
prescribed by your doctor.
Treatment may lower the chance for
Do not use any supplements or blood clots, heart disease, and stroke.
medications without checking with Treatment also lessens the chance of
your metabolic doctor. eye problems. However, even when
treated, some people still develop lens
4. Blood and urine tests
dislocation. This can often be corrected
Your child will have regular blood and
by surgery or other methods.
urine tests to check his or her amino
acid levels. Your childs diet or formula Children who begin treatment later in
may need to be adjusted based on life may have mental retardation and
blood test results. behavior problems.

55 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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What causes the CBS enzyme to be condition themselves. Instead, each


absent or not working correctly? parent has a single non-working gene
Genes tell the body to make various for homocystinuria. They are called
enzymes. People with homocystinuria carriers. Carriers do not have the
have a pair of genes that do not work condition because the other gene of
correctly. Because of the changes in this pair is working correctly.
this pair of genes, the CBS enzyme
When both parents are carriers, there
either does not work properly or is not
is a 25% chance in each pregnancy for
made at all.
the child to have homocystinuria.
How is homocystinuria inherited? There is a 50% chance for the child to
This condition is inherited in an be a carrier, just like the parents. And,
autosomal recessive manner. It affects there is a 25% chance for the child to
both boys and girls equally. have two working genes.

Everyone has a pair of genes that make Genetic counseling is available to families
the CBS enzyme. In children with who have children with this condition.

homocystinuria, neither of these genes Genetic counselors can answer your


questions about how it is inherited, options
works correctly. These children inherit
during future pregnancies, and how to test
one non-working gene for the condition
other family members. Ask your doctor
from each parent.
about a referral to a genetic counselor.

Parents of children with


Is genetic testing available?
homocystinuria rarely have the

56 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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Homocystinuria is confirmed by
special blood and urine tests. People
with this condition usually have high
levels of homocystine and methionine
in their blood. Their urine usually has
high levels of homocystine.

The condition can also be confirmed


by testing the CBS enzyme in a skin
sample.

Can you test during pregnancy?


If both gene changes have been found
in your child, DNA testing can be done
during future pregnancies. The sample
needed for this test is obtained by
either CVS or amniocentesis.

If DNA testing would not be helpful,


Genetic testing can be done on a blood an enzyme test can be done using cells
sample. Genetic testing, also called from the fetus. The sample needed for
DNA testing, looks for changes in the this test is obtained by amniocentesis.
pair of genes that cause
homocystinuria. Parents may either choose to have
testing during pregnancy or wait until
DNA testing is not necessary to birth to have the baby tested. A genetic
diagnose your child. It can be helpful counselor can talk to you about your
for carrier testing or prenatal testing, choices and answer questions about
discussed below. prenatal testing or testing your baby
after birth.
What other testing is available?

57 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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Can other members of the family All states offer newborn screening for
have homocystinuria or be carriers? homocystinuria. However, when both
parents are carriers, newborn
Having homocystinuria
screening results are not sufficient to
If they are healthy and growing
rule out the condition in a newborn
normally, older brothers and sisters of
baby. In this case, special diagnostic
a baby with homocystinuria are
testing should be done in addition to
unlikely to be affected. However,
newborn screening.
finding out whether other children in
the family have the condition may be Can other family members be tested?
important. Early treatment could
Diagnostic testing
prevent serious health problems. Ask
Brothers and sisters can be tested
your metabolic doctor whether your
using blood, urine or skin samples.
other children should be tested.

Carrier testing
Homocystinuria carriers If both gene changes have been found
Brothers and sisters who do not have in your child, other family members
the condition still have a chance to be
can have DNA testing to see if they are
carriers like their parents. Except in
carriers.
special cases, carrier testing should
only be done in people over 18 years of If DNA testing would not be helpful,
age. other methods of carrier testing may be
available. Your metabolic doctor or
Each of the parents brothers and
genetic counselor can answer your
sisters has a 50% chance to be a questions about carrier testing.
carrier. It is important for other family
members to be told that they could be Where can Confirmatory Testing be
carriers. There is a chance they are done for this condition?
also at risk to have children with
homocystinuria.

58 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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The confirmatory testing for the people with Irish ancestry. About one
disorder is done by estimation of Blood in every 50,000 babies in these groups
Homocysteine level. has homocystinuria.

Enzyme activity of CBS can be


measured for definitive and
Does homocystinuria go by any other
confirmatory diagnosis of liver biopsy,
names?
skin biopsy or long term cultured
lymphocytes and cultured skin
Homocystinuria is also called:
fibroblast.
Homocystinemia
Center
Cystathionine beta-synthase
PreventiNe Lifecare Pvt. Ltd.
deficiency
RPT House, Plot No. 6, Sector 24,
CBS deficiency
Turbhe, Navi Mumbai 400705
Ph: 022-61980000/11 Where can I find more information?
Children Living with Inherited
How many people have
Metabolic Diseases (CLIMB)
homocystinuria? http://www.climb.org.uk

About one in every 200,000 to one in


Genetic Alliance
every 300,000 babies in the United
http://www.geneticalliance.org
States is born with homocystinuria.

Does homocystinuria happen more


often in a certain ethnic group?
This condition occurs in all ethnic
groups around the world. It is found
more often in white people from the
New England region of the United
States. It is also more common in

59 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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M
What is the cost of the
aple Syrup

confirmatory test?
Urine Disease How many people have MSUD?
Does MSUD happen more often in
a certain ethnic group?
Does MSUD go by any other
Disorder name: Maple Syrup Urine
names?
Disease
Where can I find more
Acronym: MSUD Type 1A
information?

What is MSUD?
This fact sheet has information about
What causes MSUD?
MSUD. Every child is different and
If MSUD is not treated, what
some of these facts may not apply to
problems occur?
your child specifically. Certain
What is the treatment for MSUD?
treatments may be recommended for
What happens when MSUD is
some children but not others. All
treated?
children with MSUD should be
What causes the BCKAD enzymes
followed by a metabolic doctor in
to be absent or not working
addition to their primary doctor.
correctly?
How is MSUD inherited? What is MSUD?
Is genetic testing available? MSUD stands for maple syrup urine
What other testing is available? disease. It is named for the sweet
Can you test during pregnancy? maple syrup smell of the urine in
Can other members of the family untreated babies. This condition is one
have MSUD or be carriers? type of amino acid disorder. People
Can other family members be with MSUD have problems breaking
tested? down certain amino acids found in
Where can Confirmatory Testing protein.
be done for this condition?

60 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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What causes MSUD? into smaller parts called amino acids.


In order for the body to use protein Special enzymes then make changes to
from the food we eat, it is broken down the amino acids so the body can use
them.
Amino Acid Disorders:
Classic MSUD, the most common form,
Amino acid disorders (AAs) are a is caused by the absence of a group of
group of rare inherited conditions. enzymes called branched-chain
They are caused by enzymes that do
not work properly.

Protein is made up of smaller


building blocks called amino acids.
A number of different enzymes are
needed to process these amino acids
for use by the body. Because of
missing or non-working enzymes,
people with amino acid disorders
cannot process certain amino acids.
These amino acids, along with other
toxic substances, then build up in
the body and cause problems.

The symptoms and treatment vary


between different amino acid
disorders. They can also vary from
person to person with the same ketoacid dehydrogenase (BCKAD).

amino acid disorder. See the fact The job of this enzyme group is to

sheets for each specific amino acid break down three different amino acids

disorder. called leucine, isoleucine and valine.


When they cannot be broken down,
Amino acid disorders are inherited
61 autosomal NEWBORN
in an recessive SCREENING-
manner SCREEN EARLY TREAT EARLY
and affect both Unauthorised reproduction of this article is prohibited
males and females.
BABYSHIELD TMS FACT SHEET

these amino acids build up in the blood poor appetite


and cause problems. weak suck
weight loss
Leucine, isoleucine, and valine are
high pitched cry
called branched-chain amino acids
urine that smells like maple
(BCAAs) because of their tree-like
syrup or burnt sugar
structure. They are found in all foods
that contain protein. Large amounts are Babies with MSUD have episodes of
found in meat, eggs, milk, and other illness called metabolic crisis. Some of
dairy foods. Smaller amounts are found the first symptoms of a metabolic crisis
in flour, cereal, and in some vegetables are:
and fruits. extreme sleepiness
sluggishness
If MSUD is not treated, what
irritable mood
problems occur?
vomiting
There are a number of different forms
of MSUD. The most common form, If not treated, other symptoms can
classic MSUD, can be life- follow:
threatening and must be treated episodes where muscles tone
promptly to prevent serious health alternates between being rigid
problems. Other forms, including and floppy
intermediate and intermittent forms swelling of the brain
of MSUD, are less severe. These milder seizures
forms are less common. This fact sheet high levels of acidic substances
contains information on classic in the blood, called metabolic
MSUD. acidosis
coma, sometimes leading to
Classic MSUD
death
Symptoms start as soon as a baby is
fed protein, usually shortly after birth. Symptoms of a metabolic crisis often
Some of the first symptoms are: happen:

62 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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after going too long without food 1. Medical Formula


during illness or infection In addition to a low-protein diet,
during stressful events such as children are often given a special
surgery medical formula as a substitute for
milk. This formula gives them the
Without treatment, brain damage can
nutrients and protein they need while
occur. This can cause mental
helping keep their BCAA levels in a
retardation or spasticity. Some babies
safe range.
become blind. If not treated, most
babies die within a few months. Your metabolic doctor and dietician
will tell you what type of formula is
What is the treatment for MSUD?
best and how much to use. nbsp;
Your babys doctor will work with a
metabolic doctor and dietician to care 2. Diet low in branched-chain amino
for your child. acids
The diet is made up of foods that are
Prompt treatment is needed to prevent
very low in the BCAAs. This means
mental retardation and serious medical
your child will need to avoid foods
problems. Most children need to eat a
such as cows milk, regular formula,
very low-protein diet and drink a
meat, fish, cheese and eggs. Regular
special medical formula. You should
flour, dried beans, nuts, and peanut
start the diet and the formula as soon
butter also have BCAAs and must be
as you know your child has MSUD.
avoided or strictly limited.
Your dietician can create a food plan
that contains the right amount of Many vegetables and fruits have only
protein, nutrients, and energy to keep small amounts of the BCAAs and can
your child healthy. be eaten in carefully measured
amounts.
The following are treatments often
recommended for children with MSUD: There are other medical foods such as
special low-protein flours, pastas, and

63 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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rice that are made especially for people 4. Tracking BCAA levels
with MSUD. Some states offer help Your child will have regular blood tests
with payment, or require private to measure amino acid levels. The diet
insurance coverage for medical formula and formula may need to be adjusted
and other special medical foods. based on blood test results.

Your metabolic doctor and dietician 5. Call your doctor at the start of any
will decide on the best food plan for illness
your child. The exact plan will depend For children with MSUD, even minor
on many things such as your childs illness can cause a metabolic crisis. In
age, weight, and general health. Your order to prevent problems, call your
dietician will fine-tune the diet over doctor right away when your child has
time. Any diet changes should be made any of the following:
under the guidance of a dietician.
- Poor appetite
Lifelong treatment with the MSUD diet - low energy or extreme
is necessary. Children are at risk for sleepiness
episodes of metabolic crisis when they - vomiting
dont follow the diet. - an infection or illness
- a fever
3. Supplements
- behavior or personality
Children with a rare form of MSUD,
changes
called thiamine-responsive MSUD,
- difficulty walking or balance
can often be helped by thiamine
problems
supplements. Some children with
classic MSUD may also benefit from Children with MSUD need to eat more
thiamine. Ask your doctor whether carbohydrates and drink more fluids
your child should take thiamine during any illness even if theyre not
supplements. Do not use any hungry or they could have a
supplements without checking with metabolic crisis. Children who are sick
your doctor. may not want to eat. If they cant eat, or

64 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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if they show signs of a metabolic crisis, be discussed very thoroughly with your
they may need to be treated in the childs physicians.
hospital.
What happens when MSUD is
Ask your metabolic doctor if you treated?
should carry a special travel letter with With prompt and lifelong treatment,
medical instructions for your childs children with MSUD often have healthy
care. lives with typical growth and
development. Early treatment can help
6. Liver transplantation
prevent brain damage and mental
Liver transplant surgery is an optional
retardation.
treatment for people with MSUD. The
BCKAD enzyme that causes MSUD is However, children with MSUD are at
located in the liver. Because of this, increased risk to have attention deficit
some children with MSUD have had hyperactivity disorder (ADHD), anxiety
liver transplantation surgery (removal and depression even if they have had a
of their liver and replacement with a liver transplant. The reasons for this
donor liver) to treat their MSUD are not well understood at this time.
symptoms.
Even with treatment, some children
This major surgical procedure is still develop swelling of the brain or
associated with risks, and individuals have episodes of metabolic crisis.
who have had a liver transplant must Children who have repeated metabolic
take medication for the rest of their crises may develop permanent brain
lives to prevent their body from damage. This can cause lifelong
rejecting the donor liver. However, learning problems, mental retardation
successful liver transplantation cures or spasticity.
people of their MSUD symptoms.
What causes the BCKAD enzymes to
Many factors must be considered be absent or not working correctly?
before surgery and this option should

65 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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Genes tell the body to make various When both parents are carriers, there
enzymes. People with MSUD have a is a 25% chance in each pregnancy for
pair of genes that do not work the child to have MSUD. There is a
correctly. Because of these gene 50% chance for the child to be a carrier,
changes, the BCKAD enzymes do not just like the parents. And, there is a
work properly or are not made at all. 25% chance for the child to have two
working genes.
How is MSUD inherited?
MSUD is inherited in an autosomal Genetic counseling is available to
recessive manner. It affects both boys families who have children with
and girls equally. MSUD. Genetic counselors can answer
your questions about how the condition
In children with MSUD, a pair of genes
is inherited, choices during future
needed to make the BCKAD enzymes is
pregnancies, and how to test other
not working correctly. These children
family members. Ask your doctor about
inherit one non-working gene for
a referral to a genetic counselor.
MSUD from each parent.
Is genetic testing available?
Parents of children with MSUD rarely
Genetic testing for MSUD can be done
have the condition themselves. Instead,
on a blood sample. Genetic testing,
each parent has a single non-working
also called DNA testing, looks for
gene for MSUD. They are called
changes in the pair of genes that
carriers. Carriers do not have MSUD
causes MSUD.
because the other gene of this pair is
working correctly.

66 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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DNA testing is not necessary to have questions about testing for


diagnose your child. It can be helpful MSUD.
for carrier testing or prenatal testing,
Can you test during pregnancy?
discussed below.
If both gene changes have been found
in your child, DNA testing can be done
during future pregnancies. The sample
needed for this test is obtained by
either CVS or amniocentesis.

If DNA testing would not be helpful, an


enzyme test can be done on cells from
the fetus. Again, the sample needed for
this test is obtained by either CVS or
amniocentesis.

Parents may choose to have testing


during pregnancy or wait until birth to
have the baby tested. A genetic
counselor can talk to you about your
choices and answer questions about
prenatal testing or testing your baby
after birth.

What other testing is available?


Can other members of the family
MSUD can be confirmed by measuring
have MSUD or be carriers?
the amount of the branched chain
amino acids in a blood sample. It can Having MSUD
also be diagnosed by an enzyme test If they are healthy and growing
using a blood or skin sample. Talk to normally, older brothers and sisters of
your doctor or genetic counselor if you a baby with MSUD are unlikely to have

67 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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the condition. If you have questions Can other family members be tested?
about testing your other children, talk
Diagnostic testing
with your metabolic doctor or genetic
If there is concern about whether they
counselor.
have the condition, diagnostic testing
MSUD Carriers can be done on brothers or sisters. Talk
Brothers and sister who do not have to your metabolic doctor if you have
MSUD still have a chance to be carriers questions about testing for MSUD.
like their parents. Except in special Carrier testing
cases, carrier testing should only be If both gene changes have been found
done on people over 18 years of age. in your child, other family members
can have DNA testing to see if they are
Each of the parents brothers and
carriers.
sisters has a 50% chance to be a
carrier. It is important for other family If DNA testing is not helpful, other
members to be told that they could be methods of carrier testing may be
carriers. There is a small chance they available. If you have questions about
are also at risk to have children with carrier testing, ask your genetic
MSUD. counselor or metabolic doctor.

All states offer newborn screening for Where can Confirmatory Testing be
MSUD. However, when both parents done for this condition?
are carriers, newborn screening results The confirmatory test for the
are not sufficient to rule out the diagnosis of the disorder is done by
condition in a newborn baby. In this Gas Chromatography Mass
case, special diagnostic testing should Spectrometry (GC/MS) using urine
be done in addition to newborn sample.
screening. It is very important that this
testing be done shortly ideally at 24
hours of age.
Center

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PreventiNe Lifecare Pvt. Ltd. There are a number of other forms of


RPT House, Plot No. 6, Sector 24, MSUD that are less common than the
Turbhe, Navi Mumbai 400705 classic type. These other forms are not
Ph: 022-61980000/11 discussed in this fact sheet.
Intermittent branched-chain
How many people have MSUD?
ketoaciduria
About one in every 200,000 babies in
Intermediate branched-chain
the United States is born with MSUD.
ketoaciduria
Does MSUD happen more frequently Thiamine responsive MSUD
in a certain ethnic group? MSUD Type 1B
MSUD Type II
MSUD occurs in all ethnic groups. It is
more common in Mennonite people in Where can I find more information?
certain parts of the United States. In
The MSUD Family Support Group
the U.S., about one in 380 babies of
http://www.msud-support.org/
Mennonite background is born with
MSUD. It is also more common in
CLIMB (Children Living with Inherited
people of French-Canadian ancestry.
Metabolic Disorders)
http://www.climb.org.uk
Does MSUD go by any other names?
MSUD is sometimes also called:
Genetic Alliance
http://www.geneticalliance.org/
branched chain ketoaciduria
branched chain alpha-keto
dehydrogenase deficiency
BDKD deficiency
Maple Syrup Disease
Branched Chain Ketoacid
Dehydrogenase deficiency
BCKD deficiency

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P
Does PKU happen more often in a
henylketonuria

certain ethnic group?


Disorder name: Does PKU go by any other
Phenylketonuria names?
Acronym: PKU Where can I find more
information?
What is PKU?
What causes PKU? This fact sheet contains general
If PKU is not treated, what information about PKU. Every child is
problems occur? different and some of these facts may
What is the treatment for PKU? not apply to your child specifically.
What happens when PKU is Certain treatments may be advised for
treated? some children but not others. All
What causes the PAH enzyme to children with PKU should be followed
be absent or not working by a metabolic doctor in addition to
correctly? their primary care provider.
How is PKU inherited?
If your newborn has had a
Is genetic testing available?
presumptive positive screen for PKU
What other testing is available?
as a result of newborn screening, it
Can you test during pregnancy?
Can other members of the family does not yet mean that he or she has
PKU. There are other tests that need to
have PKU or be carriers?
be done to confirm whether your baby
Can other family members be
tested? actually has PKU. Some babies are
found not to have PKU and do not need
Where can Confirmatory Testing
treatment. Others are found to have a
done for this condition?
milder condition called
What is the cost of the
hyperphenylalaninemia - also called
confirmatory test?
hyperphe or non-PKU HPA. Many
How many people have PKU?

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children with non-PKU HPA do not There is also another form of non-PKU
need treatment. HPA that is treated with a medication
called BH4 (tetrahydrobiopterin). This
condition is rare (less than 2% of
Amino Acid Disorders:
cases). Blood and urine tests can be
done to determine whether your child
Amino acid disorders (AAs) are a
has this form of non-PKU hyperphe.
group of rare inherited conditions.
They are caused by enzymes that do
This fact sheet contains information
not work properly.
about classic PKU only. Therefore, the
details below are relevant only to
Protein is made up of smaller building
babies who have been confirmed to
blocks called amino acids. A number
have classic PKU. It does not contain
of different enzymes are needed to
information on non-PKU HPA or other
process these amino acids for use by
variants.
the body. Because of missing or non-
working enzymes, people with amino
acid disorders cannot process certain What is PKU?

amino acids. These amino acids, PKU stands for phenylketonuria. It is

along with other toxic substances, one type of amino acid disorder. People

then build up in the body and cause with PKU have problems breaking

problems. down an amino acid called


phenylalanine from the food they eat.
The symptoms and treatment vary
between different amino acid What causes PKU?

disorders. They can also vary from In order for the body to use protein

person to person with the same amino from the food we eat, it is broken down

acid disorder. See the fact sheets for into smaller parts called amino acids.

each specific amino acid disorder. Special enzymes then make changes to
the amino acids so the body can use
Amino acid disorders are inherited in them.
an autosomal recessive manner and
affect
71both males and females.
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PKU occurs when an enzyme, called Babies with PKU seem perfectly
phenylalanine hydroxylase (PAH), is normal at birth. The first effects are
either missing or not working properly. usually seen around 6 months of age.
The job of this enzyme is to chemically Untreated infants may be late in
change the amino acid phenylalanine learning to sit, crawl and stand. They
(Phe pronounced fee) into other may pay less attention to things around
substances. When a child with PKU them. Without treatment, a child with
eats food containing Phe, it builds up PKU will have mental retardation.
in the blood and causes problems. Phe
Some of the effects of untreated PKU
is found in almost every food, except
include:
pure fat and sugar.

mental retardation
behavior problems
hyperactivity
restlessness or irritability
seizures
a skin condition called eczema
a musty or mousy body odor
fair hair and skin

What is the treatment for PKU?


Your babys primary doctor will work
with a metabolic doctor and a dietician
experienced with PKU to care for your
child.

Prompt treatment is needed to prevent


mental retardation. Newborns need to
If PKU is not treated, what problems drink a special medical formula. It is
occur? still possible to breastfeed your baby as

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long as you get help from your best and how much to use. Some states
dietician. Babies who are breastfed offer help with payment, or require
usually need the medical formula as private insurance coverage for the
well. formula and other special medical
foods.
Most children need to eat a special diet
made up of very low-protein foods, 2. Low-Phe food plan
special medical foods, and the special The low-Phe food plan is made up of
formula. You must start the low-Phe foods that are very low in Phe. This
diet as soon as you know your child means your child must avoid or strictly
has PKU. Your dietician will create a limit the following foods:
food plan that contains the right
milk and all dairy products
amount of protein, nutrients, and
including cheese, yogurt, ice
energy to keep your child healthy. The
cream
diet should be continued throughout
regular formula
life.
meat and poultry
The following are treatments often fish
advised for children with PKU: eggs
nuts and peanut butter
1. Medical formula
dried beans
Even though they need less Phe,
regular flour
children with PKU still need a certain
amount of protein. The medical formula It is very important that your child
gives babies and children with PKU the avoid the sugar substitute aspartame
nutrients and protein they need while (sold under the brand names Equal,
helping keep their Phe levels within a Nutrasweet Sweetmate,
safe range. Canderal). Aspartame contains high
amounts of Phe. It can quickly raise the
Your metabolic doctor and dietician
blood levels of Phe in people with PKU.
will tell you what type of formula is
Your child must not have any diet

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foods or drinks that contain bone loss (osteopenia)


aspartame. Some medicines and tremors
vitamins also contain aspartame. If
Women need to be on the low-Phe diet
youre not sure, ask your pharmacist,
before becoming pregnant. They need
metabolic doctor or dietician.
to stay on the diet throughout
Many vegetables and fruits have only pregnancy. This will lessen the chance
small amounts of Phe and can be eaten for serious health and learning
in carefully measured amounts. In problems in their babies.
addition, there are other medical foods
3. Tracking Phe levels
such as low-Phe flours, baking mixes,
Babies and young children with PKU
breads, and pastas that are made
need to have regular blood tests to
especially for people with PKU.
measure their Phe levels. If there is too
Your childs food plan will depend on much or too little Phe in the blood, the
many things such as his or her age, diet and formula may need to be
weight, general health, and blood test adjusted.
results. Your dietician will fine-tune
4. BH4 supplements
your childs diet over time.
BH4 (tetrahydrobiopterin) is a
Your child should follow this diet substance made by the body. It works
throughout life. Adults who do not stay to help the PAH enzyme change Phe
on the diet and have high levels of Phe into Tyr.
in their blood may notice some of the
Some children with PKU will benefit
following:
from taking BH4 supplements in pill
trouble paying attention form. This treatment is helpful in
problems making good decisions reducing blood Phe levels in some
slow thinking children with PKU. About 10% of
irritability children with classic PKU respond to
eczema

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BH4 pills. Most children with mild Women with PKU who want to have
PKU are helped by BH4 pills. children need to have very low blood
Phe levels before they get pregnant.
Your doctor can do blood tests to
During pregnancy, they need to:
determine whether your child responds
to BH4 supplements. Do not take this stay on the low-Phe diet
supplement unless advised by your visit their PKU clinic on a
metabolic doctor. regular basis
have their blood Phe levels
5. Pregnancy in women with PKU
checked often
(Maternal PKU)
Women with PKU who are not on the What happens when PKU is treated?
low-Phe diet when they become Children with PKU who start treatment
pregnant have a high chance of having soon after birth and keep their Phe
babies with birth defects and mental levels within the suggested range
retardation. usually have normal growth and
intelligence. Some children, even when
Women who are not on the diet usually
treated, have problems with school
have high levels of Phe in their blood.
work and may need extra help.
The extra Phe gets to the fetus and
causes problems with brain and body If treatment is not started until several
growth. Babies of untreated mothers weeks after birth, delays or learning
may have the following: problems may occur. The level of delay
varies from child to child.
small brains
mental retardation Children who start treatment after 6
birth defects of the heart months of age often have mental
low birth weight retardation. Treatment is still
important, even if started late, because
This condition is called maternal PKU
it can help control behavior and mood
syndrome.

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problems and can prevent further other gene of this pair is working
damage to the brain. correctly.

What causes the PAH enzyme to be When both parents are carriers, there
absent or not working correctly? is a 25% chance in each pregnancy for
Genes tell the body to make various the child to have PKU. There is a 50%
enzymes. People with PKU have a pair chance for the child to be a carrier, just
of genes that do not work correctly. like the parents. And, there is a 25%
Because of the changes in this pair of chance for the child to have two
genes, the PAH enzyme either does not working genes.
work properly or is not made at all.

How is PKU inherited?

PKU is inherited in an autosomal


recessive manner. It affects both boys
and girls equally.

Everyone has a pair of genes that make


the PAH enzyme. In children with PKU,
neither of these genes works correctly.
These children inherit one non-working
gene for the condition from each
parent.

Parents of children with PKU rarely


have the condition themselves. Instead,
each parent has a single non-working
Genetic counseling is available to
gene for PKU. They are called carriers.
families who have children with PKU.
Carriers do not have PKU because the
Genetic counselors can answer your
questions about how PKU is inherited,

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choices during future pregnancies, and If both gene changes have been found
how to test other family members. Ask in your child with PKU, DNA testing
your doctor about a referral to a genetic can be done during future pregnancies.
counselor. The sample needed for this test is
obtained by either CVS or
Is genetic testing available?
amniocentesis.

Genetic testing for PKU can be done on


Parents may choose to have testing
a blood sample. Genetic testing, also
during pregnancy or wait until birth to
called DNA testing, looks for changes
have the baby tested. A genetic
in the pair of genes that causes PKU.
counselor can talk to you about your
choices and answer questions about
DNA testing is not necessary to
prenatal testing or testing your baby
diagnose your child. It is sometimes
after birth.
helpful to know the gene changes in a
child with PKU because it may help the
Can other members of the family
doctors and dietician develop the best
have PKU or be carriers?
treatment plan. It is sometimes of help
in determining which children will Having PKU
respond to biopterin supplements. It If they are healthy and developing
can also be helpful for carrier or normally, older brothers and sisters of
prenatal testing, discussed below. a baby with PKU are unlikely to have
PKU. Talk to your doctor or genetic
What other testing is available?
counselor if you have questions about
PKU is confirmed by measuring the
your other children.
amount of Phe and Tyr in a blood
sample. Talk to your doctor or your PKU carriers
genetic counselor if you have questions Brothers and sisters who do not have
about testing for PKU. PKU still have a 2/3rds chance to be
carriers like their parents. Except in
Can you test during pregnancy?
special cases, carrier testing should

77 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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only be done in people over 18 years of about testing for PKU.


age. Carrier testing
If both gene changes have been found
Each of the parents brothers and
in your child, other family members
sisters has a 50% chance to be a
can have DNA testing to see if they are
carrier. It is important for other family
carriers. If DNA testing is not helpful,
members to be told that they could be
other methods of carrier testing may be
carriers. There is a small chance they
available. If you have questions about
are also at risk to have children with
carrier testing, ask your genetic
PKU.
counselor or metabolic doctor.

All states offer newborn screening for


Where can Confirmatory Testing be
PKU. However, when both parents are
done for this condition?
carriers, newborn screening results are
The confirmatory test for the diagnosis
not sufficient to rule out the condition
of the disorder is done by Gas
in a newborn baby. In this case, special
Chromatography Mass Spectrometry
diagnostic testing should be done in
(GC/MS) using urine sample.
addition to newborn screening. It is
very important that this testing be done
Center
immediately ideally at 24 hours of
PreventiNe Lifecare Pvt. Ltd.
age.
RPT House, Plot No. 6, Sector 24,
Turbhe, Navi Mumbai 400705
Can other family members be tested?
Ph: 022-61980000/11
Diagnostic testing
How many people have PKU?
If there is concern about whether they About one in every 10,000 Caucasian
have the condition, your other children babies in the United States is born with
can be tested. Talk to your doctor or PKU.
genetic counselor if you have questions
Does PKU happen more frequently in
a certain ethnic group?

78 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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PKU happens in people of all ethnic dihydropteridine reductase


groups around the world. It happens (DHPR) deficiency
more often in people whose families Guanosine triphosphate
come from Ireland and other parts of cyclohydrolase (GTPCH)
Northern Europe. It is also more deficiency
common in people from Turkey and 6-pyruvoyl tetrahydrobiopterin
those who are Native Americans. PKU synthase (PTPS) deficiency
is less common in people of African, Pterin-4 acarbinolamine
Japanese or Ashkenazi Jewish dehydratase (PCD) deficiency
backgrounds.
Where can I find more information?
About 1 in every 50 Caucasians is a
Children's PKU network
PKU carrier.
http://www.pkunetwork.org/
Does PKU go by any other names?
National PKU Alliance
PKU is sometimes also called: http://www.npkua.org/

hyperphenylalaninemia classic National PKU News


type http://www.pkunews.org
phenylalanine hydroxylase
Children Living with Inherited
deficiency
Metabolic Diseases (CLIMB)
PAH deficiency
http://www.climb.org.uk
Some variants of
Genetic Alliance
hyperphenylalaninemia not discussed
http://www.geneticalliance.org
in this fact sheet are:

hyperphenylalanemia mild
type (non PKU-HPA)
biopterin deficiency

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T
What is the cost of the
yrosinemia, type

confirmatory test?
1 How many people have
tyrosinemia 1?
Does tyrosinemia 1 happen more
often in a certain ethnic group?
Disorder name: Tyrosinemia, type 1
Does tyrosinemia 1 go by any
Acronym: FAH deficiency
other names?
Where can I find more
What is tyrosinemia 1?
information?
What causes tyrosinemia 1?
If tyrosinemia 1 is not treated,
This fact sheet contains general
what problems occur?
information about tyrosinemia 1. Every
What is the treatment for
child is different and some of these
tyrosinemia 1?
facts may not apply to your child
What happens when tyrosinemia
specifically. Certain treatments may be
1 is treated?
recommended for some children but
What causes the FAH enzyme to
not others. All children with this
be absent or not working
condition should be followed by a
correctly?
metabolic doctor in addition to their
How is tyrosinemia 1 inherited?
primary doctor.
Is genetic testing available?
What other testing is available? What is tyrosinemia 1?
Can you test during pregnancy?
This condition is one type of amino
Can other members of the family
acid disorder. People with tyrosinemia
have tyrosinemia 1 or be carriers?
1 have problems breaking down an
Can other family members be
amino acid called tyrosine from the
tested?
food they eat. If not treated, the
Where can Confirmatory Testing
condition causes severe liver disease
be done for this condition?
and other serious health problems.

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What causes tyrosinemia 1? Special enzymes then make changes to


In order for the body to use protein the amino acids so the body can use
from the food we eat, it is broken down them.
into smaller parts called amino acids.
Tyrosinemia 1 occurs when an enzyme,
called fumarylacetoacetase (FAH), is
Amino Acid Disorders:
either missing or not working properly.
Amino acid disorders (AAs) are a When FAH is not working, it cannot
group of rare inherited conditions. break down tyrosine. Tyrosine and
They are caused by enzymes that do other harmful substances then build up
not work properly. in the blood. One of these substances
is called succinylacetone. When it
Protein is made up of smaller building
builds up in the blood, it causes serious
blocks called amino acids. A number liver and kidney damage. It may also
of different enzymes are needed to cause episodes of weakness or pain.
process these amino acids for use by
the body. Because of missing or non-
working enzymes, people with amino
acid disorders cannot process certain
amino acids. These amino acids,
along with other toxic substances,
then build up in the body and cause
problems.

The symptoms and treatment vary


between different amino acid
disorders. They can also vary from
person to person with the same amino
acid disorder. See the fact sheets for
each specific amino acid disorder.

Amino acid disorders are inherited in


NEWBORN SCREENING- SCREEN EARLY TREAT EARLY
an 81
autosomal recessive manner and
Unauthorised
affect both males reproduction of this article is prohibited
and females.
BABYSHIELD TMS FACT SHEET

life. Some of the first symptoms may


be:

diarrhea and bloody stools


vomiting
poor weight gain
extreme sleepiness
irritability
cabbage-like odor to the skin
or urine

Liver problems are common. They can


lead to:

enlarged liver
yellowing of the skin
tendency to bleed and bruise
easily

If tyrosinemia 1 is not treated, what swelling of the legs and

problems occur? abdomen

The symptoms can vary a great deal


Kidney problems also happen and can
from person to person. There are two
lead to:
types of tyrosinemia 1. The more
rickets, a bone thinning
common form happens in infants. The
condition
less common form is seen in older
delays in walking
children and adults.

Without prompt and careful treatment,


Tyrosinemia 1 in infants:
babies with severe liver and kidney
Babies usually show effects of the
problems usually die.
condition within the first few months of

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Some babies also have episodes that can prevent liver failure in most
include: children.
pain or weakness, especially in
Kidneys: Serious kidney
the legs
problems can occur in untreated
breathing problems
children. When the kidneys are
rapid heartbeat
not working properly, episodes
seizures
of vomiting, weakness and fever
coma, sometimes leading to
can happen. Rickets, a bone
death
thinning condition, may happen

Tyrosinemia 1 in children (chronic in children with kidney damage.

form): Medication can prevent kidney


Children with the chronic form usually problems in most children.
start having symptoms after two
Neurologic crises: Some children
months of age. Some of the first signs
have episodes of weakness, pain
may be trouble gaining weight and
or numbness in their arms, legs
episodes of vomiting and diarrhea.
or other parts of the body.
Over time, the condition can cause
Breathing problems and rapid
liver, kidney and nerve problems.
heartbeat may also happen.

Liver: If the condition is not Some children have seizures that


treated, a rare type of liver can lead to coma. Medication
scarring called nodular cirrhosis can stop episodes of neurologic
can happen. This gets worse crisis in most children.

over time and can lead to liver


Other: A small number of
failure. If not treated, many
children have had heart
children develop liver failure or
problems. Some have had high
liver cancer before the age of 10.
blood pressure.
Medication, when started early,

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What is the treatment for tyrosinemia Nitisinone will increase the level of
1? tyrosine in your childs blood. So, a
Your babys doctor will work with a low-tyrosine diet is a very important
metabolic doctor and dietician to care part of treatment.
for your child. Lifelong treatment is
Vitamin D is sometimes used to treat
usually needed to prevent liver and
children who have rickets.
kidney problems.

Do not take any medication without


Treatment consists of medication and a
talking with your doctor.
diet low in tyrosine and another amino
acid called phenylalanine (phe). The
low-tyrosine/phenylalanine diet is
made up of a special medical formula 2. Medical Formula
and carefully chosen foods. You must The special medical formula gives
start the treatment as soon as you babies and children the nutrients and
know your child has the condition. protein they need while helping keep
their tyrosine levels within a safe
The following treatments are often
range. Your metabolic doctor and
recommended for children with
dietician will tell you what type of
tyrosinemia type 1: formula is best and how much to use.

1. Medication
3. Low-tyrosine / phenylalanine diet:
A medication called nitisinone
The diet is made up of foods that are
(Orfadin ), also known as NTBC, is
very low in tyrosine and phenylalanine.
used to prevent liver and kidney This means your child will need to limit
damage. It also stops the neurologic
foods such as cows milk and regular
crises. The medication lessens the risk
formula. He or she will need to avoid
for liver cancer. Your child should start
meat, eggs and cheese. Regular flour,
taking Nitisinone as soon as possible. dried beans, nuts and peanut butter
Your doctor will need to write a
prescription for this medication.

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contain these amino acids and must nitisinone level


also be limited. liver and kidney function

Many vegetables and fruits have only These tests help your doctor and
small amounts of phenylalanine and dietician figure out whether any
tyrosine and can be eaten regularly in changes to the medication or diet are
carefully measured amounts. needed.

There are other medical foods such as Some experts suggest that children
special flours, pastas, and rice that are with tyrosinemia 1 have a CT or MRI
made especially for people with scan of their liver once a year to check
tyrosinemia 1. Some states offer help for scarring or cancer.
with payment, or require private
5. Liver transplantation
insurance coverage for formula and
Before nitisinone was available, liver
other special medical foods.
transplantation was one of the main
Your metabolic doctor and dietician treatments for tyrosinemia 1. Now,
will decide on the best food plan for nitisinone can prevent or reverse many
your child. The exact plan will depend of the liver problems and decreases the
on many things such as your childs risk of developing liver cancer. For
age, weight, general health, and how most children, nitisinone will delay,
well the medication is working. Your and hopefully prevent, the need for
dietician will fine-tune your childs diet liver transplant.
over time.
Liver transplantation is still an option
4. Blood, urine and other tests for those children that show signs of
Your child will have regular blood and liver cancer or liver failure. If you have
urine tests to check: questions, talk to your metabolic doctor
or doctor about the benefits and risks
amino acid levels
of transplantation.
the amount of succinylacetone

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What happens when tyrosinemia 1 is Everyone has a pair of genes that make
treated? the FAH enzyme. In children with
When treatment is started early, severe tyrosinemia 1, neither of these genes
liver, kidney, and neurologic symptoms works correctly. These children inherit
can be prevented. Children who are one non-working gene for the condition
treated usually have normal growth from each parent.
and intelligence.
Parents of children with tyrosinemia 1
If treatment is not started right away, rarely have the condition themselves.
children may have some liver or kidney Instead, each parent has a single non-
damage. Rickets may already be working gene for the condition. They
present and need to be treated. Delays are called carriers. Carriers do not have
in growth and development may also the condition because the other gene of
be present. The effects of delayed this pair is working correctly.
treatment vary from child to child.
When both parents are carriers, there
What causes the FAH enzyme to be is a 25% chance in each pregnancy for
absent or not working correctly? the child to have tyrosinemia 1. There
Genes tell the body to make various is a 50% chance for the child to be a
enzymes. People with tyrosinemia 1 carrier, just like the parents. And, there
have a pair of genes that do not work is a 25% chance for the child to have
correctly. Because of the changes in two working genes.
this pair of genes, the FAH enzyme
either does not work properly or is not
made at all.

How is tyrosinemia 1 inherited?


This condition is inherited in an
autosomal recessive manner. It affects
both boys and girls equally.

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for changes in the pair of genes that


causes this condition.

DNA testing is not necessary to


diagnose your child. It can be helpful
for carrier testing or prenatal testing,
discussed below.

What other testing is available?


This condition can be confirmed by
measuring the amount of
succinylacetone in the urine or by an
enzyme test on blood, skin or liver
samples. Talk to your metabolic doctor
if you have questions about these
tests.

Genetic Counseling is available to


Can you test during pregnancy?
families who have children with
If both gene changes have been found
tyrosinemia 1. Genetic counselors can
in your child, DNA testing can be done
answer your questions about how the
during future pregnancies. The sample
condition is inherited, choices during
needed for this test is obtained by
future pregnancies, and how to test
either CVS or amniocentesis.
other family members. Ask your doctor
about a referral to a genetic counselor. Parents may choose to have testing
during pregnancy or wait until birth to
Is genetic testing available?
have the baby tested. A genetic
Genetic testing for tyrosinemia 1 can
counselor can talk to you about your
be done on a blood sample. Genetic
choices and answer questions about
testing, also called DNA testing, looks
prenatal testing or testing your baby
after birth.

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Can other members of the family Some states do not provide newborn
have tyrosinemia 1 or be carriers? screening for tyrosinemia 1. However,
expanded newborn screening through
Having tyrosinemia 1
private labs is available for babies born
If they are healthy and developing
in states that do not screen for this
normally, older brothers and sisters of
condition.
a baby with tyrosinemia are unlikely to
be affected. However, finding out When both parents are carriers,
whether other children in the family newborn screening results are not
have this condition may be important. sufficient to rule out the condition in a
Early treatment can prevent serious newborn baby. In this case, special
health problems. Ask your metabolic diagnostic testing should be done in
doctor whether your other children addition to newborn screening.
should be tested.
Can other family members be tested?
Tyrosinemia 1 carriers
Diagnostic testing
Brothers and sisters who do not have If there is a concern, diagnostic testing
the condition still have a chance to be can be done on brothers and sisters.
carriers like their parents. Except in Talk to your metabolic doctor if you
special cases, carrier testing should have questions about testing other
only be done in people over 18 years of family members.
age.
Carrier testing
Each of the parents brothers and If both gene changes have been found
sisters has a 50% chance to be a in your child, other family members
carrier. It is important for other family can have DNA testing to see if they are
members to be told that they could be carriers.
carriers. There is a small chance they
Where can Confirmatory Testing be
are also at risk to have children with
done for this condition?
this condition.

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Assay of FAH enzyme activity can be population is born with the condition. It
done into skin fibroblast. may also occur more frequently in
people from Norway or Finland.
The confirmatory test for the diagnosis
of the disorder is done by Gas Does tyrosinemia 1 go by any other
Chromatography Mass Spectrometry names?
(GC/MS) using urine sample.
Tyrosinemia 1 is sometimes also
Center called:
PreventiNe Lifecare Pvt. Ltd.
Hereditary Infantile tyrosinemia
RPT House, Plot No. 6, Sector 24,
Hepatorenal tyrosinemia
Turbhe, Navi Mumbai 400705
Fumarylacetoacetase deficiency
Ph: 022-61980000/11
Fumarylacetoacetate hydrolase
How many people have tyrosinemia deficiency
1? FAH deficiency
Hereditary tyrosinemia type 1
About one in every 100,000 babies in
Tyrosinosis
the United States is born with this
condition. Two other forms of this condition
tyrosinemia type II and tyrosinemia
Does tyrosinemia 1 happen more
type III have different symptoms and
frequently in a certain ethnic group?
are not discussed in this fact sheet.
This condition occurs in all ethnic
groups around the world. It is found Where can I find more information?
more often in people of French-
About Tyrosinemia: New Parents'
Canadian background, especially in the
Guide
Saguenay Lac Saint-Jean region of
http://depts.washington.edu/tyros/abou
Quebec. About 1 in 20 French-
ttyr.htm
Canadians in this region are carriers.
About one in every 2000 babies in this

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Children Living with Inherited


Metabolic Diseases (CLIMB)
http://www.climb.org.uk

Genetic Alliance
http://www.geneticalliance.org

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C
What is the cost of the
arnitine

confirmatory test?
transporter How many people have CTD?
Does CTD happen more often in a
deficiency certain ethnic group?
Does CTD go by any other
Disorder Name: Carnitine transporter
names?
deficiency
Where can I find more
Acronym: CTD
information?

What is CTD?
This fact sheet contains general
What causes CTD?
information about CTD. Every child is
If CTD is not treated, what
different and some of this information
problems occur?
may not apply to your child
What is the treatment for CTD?
specifically. Not all is known about
What happens when CTD is
CTD. At present, there is no standard
treated?
treatment plan. Certain treatments may
What causes the CT enzyme to be
be recommended for some children but
absent or not working correctly?
not others. Children with CTD should
How is CTD inherited?
be followed by a metabolic doctor in
Is genetic testing available?
addition to their primary doctor.
What other testing is available?
Can you test during pregnancy? What is CTD?
Can other members of the family CTD stands for Carnitine transporter
have CTD or be carriers? deficiency. It is one type of fatty acid
Can other family members be oxidation disorder. People with CTD
tested? have problems using fat as energy for
Where can Confirmatory Testing the body.
be done for this condition?
What causes CTD?

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CTD occurs when an enzyme, called fat in food. It also helps us use fat
carnitine transporter (CT), is either already stored in the body.
missing or not working properly. This
enzymes job is to carry a substance
called carnitine into our cells. Carnitine
helps the body make energy from the

Fatty Acid Oxidation Disorders:

Fatty acid oxidation disorders (FAODs)


are a group of rare inherited
conditions. They are caused by
enzymes that do not work properly.

A number of enzymes are needed to


break down fats in the body (a process
called fatty acid oxidation). Problems
with any of these enzymes can cause a
fatty acid oxidation disorder. People
with FAODs cannot properly break
down fat from either the food they eat
Energy from fat keeps us going
or from fat stored in their bodies.
whenever our bodies run low of their
The symptoms and treatment vary main source of energy, a type of sugar
between different FAODs. They can called glucose. Our bodies rely on fat
also vary from person to person with when we dont eat for a stretch of time
the same FAOD. See the fact sheets for like when we miss a meal or when we
each specific FAOD. sleep.

FAODs are inherited in an autosomal When the normal CT enzyme is


recessive manner and affect both missing or not working well, the body

males and females.


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cannot use fat for energy. Instead, it diarrhea


must rely solely on glucose. Although vomiting
glucose is a good source of energy, hypoglycemia
there is a limited amount available.
If a metabolic crisis is not treated, a
Once the glucose has been used up, the
child with CTD can develop:
body tries to use fat without success.
breathing problems
This leads to low blood sugar, called
swelling of the brain
hypoglycemia, and to the buildup of
seizures
harmful substances in the blood.
coma, sometimes leading to
If CTD is not treated, what problems death
occur?
Babies who are not treated may have
There are two main forms of CTD: one
other effects:
begins in infancy, the other in
enlarged heart
childhood.
enlarged liver
CTD in infants muscle weakness
Babies with CTD first show symptoms anemia
between birth and age three. CTD can
Repeated episodes of metabolic crisis
cause bouts of illness called metabolic
can cause brain damage. This can
crisis. Some of the first symptoms of a
result in learning problems or mental
metabolic crisis are:
retardation.
extreme sleepiness
Symptoms of a metabolic crisis often
behavior changes
happen after having nothing to eat for
irritable mood
more than a few hours. Symptoms are
poor appetite
also more likely when a child with CTD
Other symptoms then follow: gets sick or has an infection.
fever
CTD in children
nausea

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Children with CTD appear perfectly Certain treatments may be advised for
normal until symptoms begin, usually some children but not others. When
between the ages of one and seven. necessary, treatment is usually needed
Some of the effects of childhood CTD throughout life. The following are
are: treatments often recommended for
children with CTD:
enlarged heart
muscle weakness 1. L-carnitine
if left untreated, risk of heart The main treatment for CTD is lifelong
failure and death use of L-carnitine. This is a safe and
natural substance that helps body cells
Children with this type of CTD do not
make energy. It also helps the body get
have episodes of hypoglycemia or
rid of harmful wastes. L-carnitine can
metabolic crises. Their intelligence is
reverse the heart problems and muscle
not affected.
weakness that happen in children with
CTD.
Some children with CTD deficiency
never have symptoms and are only
Your doctor will decide whether or not
found to be affected after a brother or
your child needs L-carnitine. Unless
sister is diagnosed. Many infants
you are advised otherwise, use only L-
diagnosed based on newborn
carnitine prescribed by your doctor. Do
screening results never develop
not use L-carnitine without checking
symptoms of CTD.
with your doctor.

What is the treatment for CTD?


2. Avoid going a long time without
Your baby's primary doctor will work
food
with a metabolic doctor to care for your
Infants and young children with CTD
child. Your doctor may also suggest
need to eat frequently to prevent a
that you meet with a dietician familiar
metabolic crisis. Your metabolic doctor
with CTD.
will tell you how often your child needs
to be fed. In general, it is often

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suggested that infants be fed every four child needs to have any changes in his
to six hours. Some babies need to eat or her diet.
even more frequently than this. It is
4. If your baby has CTD, call your
important that infants be fed during the
doctor at the start of any illness
night. They may need to be woken up
Always call your health care provider
to eat if they do not wake up on their
when your baby has any of the
own. Your metabolic doctor and
following:
dietician will give you an appropriate
feeding plan for your infant. Your
poor appetite
doctor will also give you a sick day
low energy or excessive
plan tailored to your childs needs for
sleepiness
you to follow during illnesses or other vomiting
times when your child will not eat.
diarrhea
an infection
Your metabolic doctor will continue to
a fever
advise you on how often your child
persistent muscle pain or
should eat as he or she gets older.
weakness
When they are well, many teens and
adults with CTD can go without food
Babies with CTD need to eat extra
for up to 12 hours without problems. starchy food and drink more fluids
The other treatments usually need to during any illness even if they may
be continued throughout life. not feel hungry or they could have a
metabolic crisis. Children who are sick
3. Diet
often dont want to eat. If they wont or
Sometimes, in addition to L-carnitine
cant eat, they may need to be treated
treatment, a low-fat, high carbohydrate
in the hospital to prevent serious health
food plan is recommended. Any diet
problems.
changes should be made under the
guidance of a dietician familiar with
Ask your metabolic doctor if you
CTD. Ask your doctor whether your should carry a special travel letter with

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medical instructions for your childs cause learning disabilities or mental


care. retardation.

What happens when CTD is treated? What causes the CT enzyme to be


With prompt and careful treatment, absent or not working correctly?
children with CTD usually live healthy Genes tell the body to make various
lives with typical growth and enzymes. People with CTD have a pair
of genes that do not work correctly.
Because of the changes in this pair of
genes, the CT enzyme does not work
properly or is not made at all.

How is CTD inherited?


CTD is inherited in an autosomal
recessive manner. It affects both boys
and girls equally.

Everyone has a pair of genes that make


the CT enzyme. In children with CTD,
neither of these genes works correctly.
These children inherit one non-working
gene for the condition from each
parent.

development. Treatment with L- Parents of children with CTD are rarely


carnitine can often reverse heart affected with the disorder. Instead,
enlargement and muscle weakness. each parent has a single non-working
gene for CTD. They are called carriers.
Babies with CTD who have repeated
Carriers do not have CTD because the
episodes of metabolic crisis may have
other gene of this pair is working
permanent brain damage. This can
correctly.

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When both parents are carriers, there can be helpful for carrier testing or
is a 25% chance in each pregnancy for prenatal diagnosis, discussed below.
the child to have CTD. There is a 50% Talk with your metabolic doctor or
chance for the child to be a carrier, just genetic counselor if you have questions
like the parents. And, there is a 25% about genetic testing for CTD.
chance for the child to have two
What other testing is available?
working genes.
CTD can be confirmed by a carnitine
Genetic counseling is available to uptake test on a skin sample. Talk to
families who have children with CTD. your doctor or genetic counselor if you
Genetic counselors can answer your have questions about genetic testing
questions about how CTD is inherited, for CTD.
choices during future pregnancies, and
Can you test during pregnancy?
how to test other family members. Ask
If both gene changes have been found
your doctor about a referral to a genetic
in the child with CTD, DNA testing can
counselor.
be done during future pregnancies. The
Is genetic testing available? sample needed for this test is obtained
Genetic testing for CTD can be done on by either CVS or amniocentesis.
a blood sample. Genetic testing, also
If DNA testing would not be helpful,
called DNA testing, looks for changes
testing during pregnancy can be
in the pair of genes that cause CTD. In
attempted by performing special tests
some affected children, both gene
on fetal cells. Again, the sample needed
changes can be found. However, in
for these tests is obtained by either
other children, neither or only one of
CVS or amniocentesis
the two gene changes can be found,
even though we know they are
Parents may either choose to have
present.
testing during pregnancy or wait until
birth to have the baby tested. A genetic
DNA testing is not necessary to
counselor can talk to you about your
diagnose your child. When available, it

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choices and answer other questions Mothers diagnosed with CTD because
you may have about prenatal testing or their infant had a positive newborn
testing your baby after birth. screen for CTD often have no
symptoms of CTD. However, it is
Can other members of the family
important that they talk to their doctor
have CTD or be carriers?
about treatment to prevent serious
health problems.
Having CTD
The brothers and sisters of a baby with
CTD carriers
CTD have a small chance of being
Brothers and sisters who do not have
affected, even if they havent had
CTD still have a chance to be carriers
symptoms. Finding out whether any
like their parents. Except in special
other children in the family have CTD
cases, carrier testing should only be
is important because early treatment
done in people over 18 years of age.
may prevent serious health problems.
Talk to your doctor or genetic Each of the parents brothers and
counselor about testing your other sisters has a 50% chance to be a CTD
children for CTD. carrier. It is important for other family
members to be told that they could be
Occasionally, a mother is diagnosed
carriers. There is a very small chance
with CTD when her infant has a
they are also at risk to have children
positive newborn screening test for
with CTD.
CTD. The babys low carnitine level at
birth is because of the mothers low Almost all states offer newborn
carnitine levels. This is a condition screening for CTD. However, expanded
called secondary carnitine deficiency. newborn screening through private
Infants with secondary carnitine labs is available for babies born in
deficiency are treated with L-carnitine states that do not screen for this
until their carnitine levels are normal. condition.
They do not need lifelong treatment.

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When both parents are carriers, Diagnostic testing for CTD


newborn screening results are not Brothers and sisters of a baby with
sufficient to rule out CTD in a newborn CTD can be tested by DNA testing
baby. In this case, special diagnostic using a blood sample or by a special
testing should be done in addition to test done on a skin sample.
newborn screening.
Mothers suspected of having CTD will
During pregnancy, women carrying have blood and urine tests to measure
fetuses with CTD may be at increased their carnitine levels. Some may also
risk to develop serious medical have a special test done on a skin
problems. Some women carrying sample or by DNA testing using a
fetuses with Fatty Acid Oxidation blood sample.
Disorders have developed:
CTD carrier testing
excessive vomiting If both gene changes have been found
abdominal pain in the child with CTD, other family
high blood pressure members can have DNA testing to see
jaundice if they are carriers.
abnormal fat storage in the liver
If DNA testing would not be helpful,
severe bleeding
other methods of carrier testing may be
All women with a family history of available. Your metabolic doctor or
CTD should share this information genetic counselor can answer your
with their obstetricians and other questions about carrier testing.
health care providers before and during
Where can Confirmatory Testing be
any future pregnancies. Knowing about
done for this condition?
these risks allows better medical care
and early treatment if needed.
The confirmatory test for the diagnosis
is done by Liquid Chromatography
Can other family members be tested?

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Mass Spectrometry (LC/MS) using Where can I find more information?


blood sample.
Fatty Oxidation Disorders (FOD)
Center Family Support Group
PreventiNe Lifecare Pvt. Ltd. http://www.fodsupport.org
RPT House, Plot No. 6, Sector 24,
Organic Acidemia Association
Turbhe, Navi Mumbai 400705
http://www.oaanews.org
Ph: 022-61980000/11

United Mitochondrial Disease


How many people have CTD?
Foundation
About one in every 50,000 babies in the http://www.umdf.org
United States is born with CTD.
Genetic Alliance
Does CTD happen more frequently in http://www.geneticalliance.org
a certain ethnic group?
Mito Action
CTD occurs in all ethnic groups. It is
http://www.mitoaction.org
more common in people from the Faroe
Islands in the United Kingdom. About 1
in 300 babies born in the Faroe Island
has CTD.

Does CTD go by any other names?

CTD is also called:

Systemic primary carnitine


deficiency (SPCD)
Systemic carnitine deficiency
(SCD)
Primary carnitine deficiency
Carnitine uptake defect (CUD)

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C
Can other family members be
arnitine

tested?
Acylcarnitine Where can Confirmatory Testing
be done for this condition?
Translocase What is the cost of the
confirmatory test?
Deficiency
How many people have CAT
deficiency?
Disorder name: Carnitine
Does CAT deficiency happen more
acylcarnitine translocase deficiency
often in a certain ethnic group?
Acronym: CAT
Does CAT deficiency go by any
What is CAT deficiency? other names?
What causes CAT deficiency? Where can I find more
If CAT deficiency is not treated, information?
what problems occur?
This fact sheet has general information
What is the treatment for CAT
about CAT deficiency. Every child is
deficiency?
different and some of this information
What happens when CAT
may not apply to your child
deficiency is treated?
specifically. Not all is known about
What causes the CAT enzyme to
CAT deficiency and, at present, there is
be absent or not working
no standard treatment plan. There may
correctly?
be treatments recommended for some
How is CAT deficiency inherited?
children but not others. Children with
Is there genetic testing available?
CAT deficiency should be followed by
What other testing is available?
a metabolic doctor in addition to their
Can you test during pregnancy?
primary doctor.
Can other members of the family
have CAT deficiency or be
What is CAT deficiency?
carriers?

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Fatty Acid Oxidation Disorders: have problems breaking down fat into
energy for the body.
Fatty acid oxidation disorders
(FAODs) are a group of rare inherited
What causes CAT deficiency?
conditions. They are caused by
CAT deficiency occurs when an
enzymes that do not work properly.
enzyme, called "carnitine acylcarnitine
A number of enzymes are needed to translocase" (CAT), is either missing or
break down fats in the body (a not working properly. This enzyme's
process called fatty acid oxidation). job is to help change certain fats in the
Problems with any of these enzymes food we eat into energy. It also helps to
can cause a fatty acid oxidation break down fat already stored in the
disorder. People with FAODs cannot body.
properly break down fat from either
the food they eat or from fat stored in
their bodies.

The symptoms and treatment vary


between different FAODs. They can
also vary from person to person with
the same FAOD. See the fact sheets
for each specific FAOD.

FAODs are inherited in an autosomal


recessive manner and affect both
males and females.

CAT deficiency stands for "carnitine


acylcarnitine translocase deficiency". It
is one type of fatty acid oxidation
Energy from fat keeps us going
disorder. People with CAT deficiency
whenever our bodies run low of their

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main source of energy, a type of sugar fever


called glucose. Our bodies rely on fat diarrhea
for energy when we don't eat for a vomiting
stretch of time - like when we miss a hypoglycemia
meal or when we sleep.
If a metabolic crisis is not treated, a
When the CAT normal enzyme is child with CAT deficiency can develop:
missing or not working well, the body muscle weakness
cannot use fat for energy, and must seizures
rely solely on glucose. Although breathing problems
glucose is a good source of energy, coma, sometimes leading to
there is a limited amount available. death
Once the glucose has been used up, the
There are two forms of CAT deficiency.
body tries to use fat without success.
The most common type happens in
This leads to low blood sugar, called
newborns. A milder, less common type
hypoglycemia, and to the build up of
happens in older infants and children.
harmful substances in the blood.

CAT deficiency in newborns


If CAT deficiency is not treated, what
Newborns with CAT deficiency often
problems occur?
show symptoms within the first week
CAT deficiency can cause episodes of
of life. Episodes of metabolic crisis are
illness called metabolic crises. Some of
common. High levels of ammonia in the
the first symptoms of a metabolic crisis
blood can occur. This can cause
are:
serious brain damage.
extreme sleepiness
Newborns with CAT may also have:
behavior changes
irritable mood
low muscle tone (floppy muscles
poor appetite and joints) and muscle
weakness
Other symptoms then follow:

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enlarged liver that you meet with a dietician familiar


heart problems and enlarged with CAT deficiency.
heart
Certain treatments may be helpful for
breathing problems
some children but not others. When
Babies who are not treated usually die necessary, treatment usually needed
of heart problems, breathing problems, throughout life. The following are
liver failure or high levels of ammonia treatments sometimes recommended
in the blood. for children with CAT deficiency:

CAT deficiency in children 1. Avoid going a long time without


Children with the mild type of CAT food
deficiency usually start having Infants and young children with CAT
symptoms before age three. They are at deficiency need to eat frequently to
risk to have episodes of metabolic prevent a metabolic crisis. Your
crisis, but usually do not have heart metabolic doctor will tell you how often
problems. your child needs to be fed. In general,
it is often suggested that infants be fed
In both types of CAT deficiency,
every four to six hours. Some babies
symptoms often happen after having
need to eat even more frequently than
nothing to eat for more than a few
this. It is important that infants be fed
hours. Symptoms are also more likely
during the night. They may need to be
when a person with CAT deficiency
woken up to eat if they do not wake up
gets sick or has an infection.
on their own. Your metabolic doctor
and dietician will give you an
What is the treatment for CAT
appropriate feeding plan for your
deficiency?
infant. Your doctor will also give you a
Your babys primary doctor will work
sick day plan, tailored to your childs
with a metabolic doctor to care for your
needs, for you to follow during
child. Your doctor may also suggest

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illnesses or other times when your under the guidance of a dietician


child will not eat. experienced with CAT deficiency.

Your metabolic doctor will continue to Ask your doctor whether your child
advise you on how often your child needs to have any changes in his or her
should eat as he or she gets older. diet.
When they are well, many teens and
2. L-carnitine and MCT oil
adults with CAT deficiency can go
Some children may be helped by taking
without food for up to 12 hours without
L-carnitine. This is a safe and natural
problems. The other treatments usually
substance that helps body cells make
need to be continued throughout life.
energy. It also helps the body get rid of
2.Diet harmful wastes.
Sometimes a low-fat, high
Your doctor will decide whether or not
carbohydrate diet is advised.
your child needs L-carnitine. Unless
Carbohydrates give the body many
you are advised otherwise, use only L-
types of sugar that can be used as
carnitine prescribed by your doctor. Do
energy. In fact, for children needing
not use L-carnitine without checking
this treatment, most food in the diet
with your doctor.
should be carbohydrates (bread, pasta,
fruit, vegetables, etc.) and protein (lean Medium Chain Triglyceride oil (MCT
meat and low-fat dairy food). Any diet
oil) is sometimes used as part of the
changes should be made under the
food plan for people with CAT
guidance of a dietician.
deficiency. This special oil has medium
chain fatty acids that people with CAT
People with CAT deficiency cannot use
deficiency can use in small amounts for
particular building blocks of fat called
energy. Your metabolic doctor or
"long chain fatty acids". A dietician can
dietician can guide you in how to use
help you create a food plan low in these
this supplement. You will need to get a
fats. Any diet changes should be made

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prescription from your doctor to get with medical instructions for your
MCT oil. childs care.

3. Call your doctor at the start of any What happens when CAT deficiency
illness is treated?
Prompt and careful treatment may help
Always call your health care provider
prevent or control symptoms in
when your child has any of the
children with CAT deficiency.
following:
However, some children continue to
have metabolic crises and other health
poor appetite
low energy or excessive problems despite treatment. Even with
treatment, there is a risk of death,
sleepiness
especially in newborns with symptoms.
vomiting
diarrhea
What causes the CAT enzyme to be
an infection
absent or not working correctly?
a fever
Genes tell the body to make various
persistent muscle pain or
enzymes. People with CAT deficiency
weakness
have a pair of genes that do not work
correctly. Because of the changes in
Children with CAT deficiency need to
eat extra starchy food and drink more this pair of genes, the CAT enzyme
either does not work properly or is not
fluids during any illness - even if they
made at all.
may not feel hungry - or they could
develop a metabolic crisis. Children
How is CAT deficiency inherited?
who are sick often dont want to eat. If
CAT deficiency is inherited in an
they wont or cant eat, children with
autosomal recessive manner. It affects
CAT deficiency may need to be treated
both boys and girls equally.
in the hospital to prevent a metabolic
crisis. Ask your metabolic doctor if Everyone has a pair of genes that make
you should carry a special travel letter the CAT enzyme. In children with CAT

106 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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deficiency, neither of these genes


works correctly. These children inherit
one non-working gene for the condition
from each parent.

Parents of children with CAT


deficiency rarely have the disorder.
Instead, each parent has a single non-
working gene for CAT deficiency. They
are called carriers. Carriers do not have
the condition because the other gene of
this pair is working correctly.

When both parents are carriers, there


is a 25% chance in each pregnancy for
the child to have CAT deficiency. There
is a 50% chance for the child to be a Genetic counseling is available to
carrier, just like the parents. And, there
families who have children with CAT
is a 25% chance for the child to have
deficiency. Genetic counselors can
two working genes. answer your questions about how CAT
deficiency is inherited, options during
future pregnancies, and how to test
other family members. Ask your doctor
about a referral to a genetic counselor.

Is there genetic testing available?


Genetic testing for CAT deficiency can
be done on a blood sample. Genetic
testing, also called DNA testing, looks
for changes in the pair of genes that

107 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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cause CAT deficiency. In some affected for these tests is obtained by either
children, both gene changes can be CVS or amniocentesis.
found. However, in other children,
Parents may either choose to have
neither or only one of the two gene
testing during pregnancy or wait until
changes can be found, even though we
birth. A genetic counselor can talk to
know they are present.
you about your choices and answer
DNA testing is not necessary to other questions about prenatal testing
diagnose your child. It can be helpful or testing your baby after birth.
for carrier testing or prenatal diagnosis,
Can other members of the family
discussed below.
have CAT deficiency or be carriers?
What other testing is available?
CAT deficiency
CAT deficiency can also be confirmed
Brothers and sisters of an affected
by a special enzyme test on a skin
baby have a chance of having CAT
sample. Talk to your doctor or genetic
deficiency, even if they haven't had
counselor if you have questions about
symptoms. Finding out whether other
testing for CAT deficiency.
children in the family have CAT
Can you test during pregnancy? deficiency is important because early
If both gene changes have been found treatment may prevent serious health
in the child with CAT deficiency, DNA problems. Talk to your doctor or
testing can be done during future genetic counselor about testing your
pregnancies. The sample needed for other children.
this test is obtained by either CVS or
CAT deficiency carriers
amniocentesis.
Brothers and sisters who do not have
If DNA testing would not be helpful, CAT deficiency still have a chance to
testing during pregnancy can be be carriers like their parents. Except in
attempted by performing special tests special cases, carrier testing should
on fetal cells. Again, the sample needed

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only be done in people over 18 years of excessive vomiting


age. abdominal pain
high blood pressure
Each of the parents' brothers and
jaundice
sisters has a 50% chance to be a carrier
abnormal fat storage in the liver
for CAT deficiency. It is important for
severe bleeding
other family members to be told that
they could be carriers. There is a very All women with a family history of
small chance they are also at risk to CAT deficiency should share this
have children with CAT deficiency. information with their obstetricians and
other health care providers before and
Some states do not offer newborn
during any future pregnancies.
screening for CAT deficiency.
Knowing about these risks allows
However, expanded newborn screening
better medical care and early treatment
is available through private labs for
if needed.
babies born in states that do not screen
for this condition. Can other family members be tested?

When both parents are carriers, Diagnostic testing for CAT deficiency
newborn screening results are not Brothers and sisters of an affected
sufficient to rule out CAT deficiency in child can be tested for CAT deficiency
a newborn baby. In this case, special using either DNA testing or a special
diagnostic testing should be done in enzyme test.
addition to newborn screening.
Carrier testing
During pregnancy, women carrying If both gene changes have been found
fetuses with CAT deficiency may be at in the child with CAT deficiency, other
increased risk to develop serious family members can have DNA testing
medical problems. Some women to see if they are carriers.
carrying fetuses with Fatty Acid
Oxidation Disorders have developed:

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If DNA testing would not be helpful, Does CAT deficiency go by any other
other methods of carrier testing may be names?
available. Your metabolic doctor or
CAT deficiency is also known as:
genetic counselor can answer your
questions about carrier testing.
carnitine acylcarnitine carrier
(CAC)
Where can Confirmatory Testing be
CACT deficiency
done for this condition?
The confirmatory test for the diagnosis
Where can I find more information?
is done by Liquid Chromatography
Mass Spectrometry (LC/MS) using Fatty Oxidation Disorders (FOD)
blood sample. Family Support Group
http://www.fodsupport.org
Center
PreventiNe Lifecare Pvt. Ltd. Organic Acidemia Association
RPT House, Plot No. 6, Sector 24, http://www.oaanews.org
Turbhe, Navi Mumbai 400705
United Mitochondrial Disease
Ph: 022-61980000/11
Foundation
How many people have CAT http://www.umdf.org
deficiency?
Children Living with Inherited
CAT deficiency is very rare. The actual
Metabolic Disorders (CLIMB)
incidence is unknown.
http://www.climb.org.uk
Does CAT deficiency happen more
Genetic Alliance
often in a certain ethnic group?
http://www.geneticalliance.org
No, CAT deficiency does not happen
more often in any specific race, ethnic
group, geographical area or country.

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C
Can other family members be
arnitine

tested?
Palmitoyl Where can Confirmatory Testing
be done for this condition?
Transferase What is the cost of the
confirmatory test?
Deficiency, type 1A
How many people have CPT-1A
deficiency?
Disorder Name: Carnitine palmitoyl
Does CPT-1A deficiency happen
transferase deficiency, type 1A
more often in a certain ethnic
Acronym: CPT-1A
group?
What is CPT-1A deficiency? Does CPT-1A deficiency go by any
What causes CPT-1A deficiency? other names?
If CPT-1A deficiency is not Where can I find more
treated, what problems occur? information?
What is the treatment for CPT-1A
This fact sheet contains general
deficiency?
information about CPT-1A deficiency.
What happens when CPT-1A
Every child is different and some of this
deficiency is treated?
information may not apply to your child
What causes the CPT-1A enzyme
specifically. Not all is known about
to be absent or not working
CPT-1A deficiency and, at present,
correctly?
there is no standard treatment plan.
How is CPT-1A deficiency
Certain treatments may be
inherited?
recommended for some children but
Is there genetic testing available?
not others. Children with CPT-1A
What other testing is available?
deficiency should be followed by a
Can you test during pregnancy?
metabolic doctor in addition to their
Can other members of the family
primary doctor.
have CPT-1A deficiency or be
carriers?

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What is CPT-1A deficiency?


for each specific FAOD.
CPT-1A deficiency stands for
carnitine palmitoyl transferase - type FAODs are inherited in an autosomal
1A deficiency. It is one type of fatty recessive manner and affect both
acid oxidation disorder. People with males and females.
CPT-1A deficiency have problems
breaking down fat into energy for the What causes CPT-1A?
body. CPT-1A deficiency occurs when an
enzyme, called carnitine palmitoyl
Fatty Acid Oxidation Disorders: transferase 1A (CPT-1A) is either
missing or not working properly. This
Fatty acid oxidation disorders
enzymes job is to help change certain
(FAODs) are a group of rare inherited
fats in the food we eat into energy. It
conditions. They are caused by
also helps break down fat already
enzymes that do not work properly.
stored in the body.

A number of enzymes are needed to


break down fats in the body (a
process called fatty acid oxidation).
Problems with any of these enzymes
can cause a fatty acid oxidation
disorder. People with FAODs cannot
properly break down fat from either
the food they eat or from fat stored in
their bodies.

The symptoms and treatment vary


between different FAODs. They can
also vary from person to person with
the same FAOD. See the fact sheets

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source of energy, there is a limited


amount available. Once the glucose
has been used up, the body tries to use
fat without success. This leads to low
blood sugar, called hypoglycemia, and
to the buildup of harmful substances in
the blood

If CPT-1A deficiency is not treated,


what problems occur?
CPT-1A deficiency can cause episodes
of illness caused metabolic crises.
Children with CPT-1A deficiency
usually start showing symptoms
between the ages of 8 and 18 months,
although effects can occur earlier.
Some of the first signs of a metabolic
crisis are:
Energy from fat keeps us going
whenever our bodies run low of their extreme sleepiness

main source of energy, a type of sugar behavior changes

called glucose. Our bodies rely on fat irritable mood

when we dont eat for a stretch of time poor appetite

like when we miss a meal or when we


Other symptoms then follow:
sleep.
fever

When the CPT-1A enzyme is missing diarrhea

or not working, the body cannot use fat vomiting

for energy, and must rely solely on hypoglycemia

glucose. Although glucose is a good high levels of ammonia in the


blood

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If a metabolic crisis is not treated, a Babies and children who are not
child with CPT-1A deficiency can treated can have:
develop:
learning problems
breathing problems
delays in walking and other
seizures
motor skills
coma, sometimes leading to
liver, heart, or kidney problems
death

Some children with CPT-1A deficiency


Between episodes of metabolic crisis,
have never had symptoms and are only
people with CPT-1A deficiency are
found to be affected after a brother or
usually healthy. However, repeated
sister has been diagnosed. CPT-1A in
episodes may cause brain damage that
people of Inuit (Native American
can result in learning problems or
Alaskan) or First Nation (Canada)
mental retardation.
ethnicity very rarely have symptoms.
Symptoms often happen after having
What is the treatment for CPT-1A
nothing to eat for more than a few
deficiency?
hours. During long periods without
eating, the glucose in the body is used
Your babys primary doctor may work
up. This causes hypoglycemia. The with a metabolic doctor to care for your
body then tries to use fat for energy, child. Your doctor may also suggest
leading to the build up of harmful
that you meet with a dietician familiar
substances in the blood. Symptoms are
with CPT-1A deficiency.
also more likely when a person with
CPT-1A deficiency gets sick or has an Certain treatments may be advised for
infection. Prompt emergency treatment some children but not others. When
of infants and children with CPT1A can necessary, treatment is usually needed
help prevent metabolic crises or lessen throughout life. The following are
their severity. treatments sometimes recommended
for children with CPT-1A deficiency:

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1. Avoid going a long time without recommended. Carbohydrates give the


food body many types of sugar that can be
Infants and young children with CPT- used as energy. In fact, for children
1A deficiency need to eat frequently to needing this treatment, most food in
prevent a metabolic crisis. Your the diet should be carbohydrates
metabolic doctor will tell you how often (bread, pasta, fruit, vegetables, etc.)
your child needs to be fed. In general, and protein (lean meat and low-fat
it is often suggested that infants be fed dairy foods). Any diet changes should
every four to six hours. Some babies be made under the guidance of a
need to eat even more frequently than dietician experienced with CPT-1A
this. Your metabolic doctor and deficiency.
dietician will give you an appropriate
People with CPT-1A deficiency cannot
feeding plan for your infant. Your
use certain building blocks of fat called
doctor will also give you a sick day
long chain fatty acids. Your dietician
plan tailored to your childs needs for
can help create a food plan low in these
you to follow during illnesses or other
fats. Much of the rest of fat in the diet
times when your child will not eat.
will likely be in the form of medium
Your metabolic doctor will continue to chain fatty acids.
advise you on how often your child
Ask your doctor if your child needs to
should eat as he or she gets older.
have any changes in his or her diet.
When they are well, many teens and
adults with CPT-1A deficiency can go
2. Medium Chain Triglyceride oil
without food for up to 12 hours without
(MCT)
problems. The other treatments usually
Medium Chain Triglyceride oil (MCT
need to be continued throughout life.
oil) is often used as part of the food
plan for people with CPT-1A
2.Diet
deficiency. This special oil has medium
Sometimes a low-fat, high
chain fatty acids that can be used for
carbohydrate food plan is
energy. A metabolic doctor or dietician

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can guide you in how to use this medical instructions for your childs
supplement. You will need to get a care.
prescription from your doctor to get
What happens when CPT-1A
MCT oil.
deficiency is treated?
3. Call your doctor at the start of any With prompt and careful treatment,
illness children with CPT-1A deficiency often
Always call your health care provider live healthy lives with typical growth
right away when your child has any of and development. After 5 years of age,
the following: metabolic crises tend to happen less
often and are not as severe.
poor appetite
low energy or excessive If repeated episodes of metabolic crisis
sleepiness occur, there is a chance for permanent
vomiting learning disabilities or mental
diarrhea retardation.
an infection
What causes the CPT-1A enzyme to
a fever
be absent or not working correctly?
Children with CPT-1A deficiency need Genes tell the body to make various
to eat extra starchy food and drink enzymes. People with SCHADD have a
more fluids than usual when they are pair of genes that do not work
sick even if they may not feel hungry correctly. People with CPT-1A
or they could have a metabolic crisis. deficiency have a pair of genes that do
Children who are sick often dont want not work correctly. Because of the
to eat. If they wont or cant eat, they changes in this pair of genes, the CPT-
may need to be treated in the hospital 1A enzyme either does not work
to prevent serious health problems. properly or is not made at all.
Ask your metabolic doctor if you
How is CPT-1A deficiency inherited?
should carry a special travel letter with

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CPT-1A deficiency is inherited in an


autosomal recessive manner. It affects
both boys and girls equally.

Everyone has a pair of genes that make


the CPT-1A enzyme. In children with
CPT-1A deficiency, neither of these
genes works correctly. These children
inherit one non-working gene for the
condition from each parent.

Parents of children with CPT-1A


deficiency are rarely affected with the
disorder. Instead, each parent has a
single non-working gene for CPT-1A
deficiency. They are called carriers.
Carriers do not have the condition Genetic counseling is available to
because the other gene of this pair is
families who have children with CPT-
working correctly.
1A deficiency. Genetic counselors can
answer your questions about how CPT-
When both parents are carriers for
1A deficiency is inherited, choices
CPT-1A deficiency, there is a 25%
during future pregnancies, and how to
chance in each pregnancy for the child
test other family members. Ask your
to have CPT-1A deficiency. There is a
doctor about a referral to a genetic
50% chance for the child to be a carrier,
counselor.
just like the parents. And, there is a
25% chance for the child to have two
Is genetic testing available?
working genes. Genetic testing for CPT-1A deficiency
can be done on a blood sample.
Genetic testing, also called DNA

117 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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testing, looks for changes in the pair of not work correctly. Because of the
genes that cause the condition. In most changes in this pair of genes, the CPT-
affected children, both gene changes 1A enzyme either does not work
can be found. However, in some properly or is not made at all.
children, neither or only one of the two
If DNA testing would not be helpful,
gene changes can be found, even
testing during pregnancy can be done
though we know they are present.
by an enzyme test on cells from the
DNA testing is not necessary to fetus. The sample needed for this test
diagnose your child. It can be helpful is obtained by either CVS or
for carrier testing or prenatal diagnosis, amniocentesis.
discussed below. Talk with your
Parents may either choose to have
metabolic doctor or genetic counselor if
testing during pregnancy or wait until
you have questions about DNA testing
birth to have the baby tested. A genetic
for CPT-1A.
counselor can talk to you about your
What other testing is available? choices and answer questions about
CPT-1A deficiency can be confirmed by prenatal testing or testing your baby
a special enzyme test on a skin sample. after birth.
Your doctor or genetic counselor can
Can other members of the family
answer your questions about testing
have CPT-1A or be carriers?
for CPT-1A deficiency.

Having CPT-1A deficiency


Can you test during pregnancy?
The brothers and sisters of an affected
If both gene changes have been found
baby have a chance of having CPT-1A
in your child with CPT-1A deficiency,
deficiency, even if they havent had
DNA testing can be done during future
symptoms. Finding out whether other
pregnancies. The sample needed for
children in the family have CPT-1A
this test is obtained by either CVS or
deficiency is important because early
amniocentesis. People with CPT-1A
treatment may prevent serious health
deficiency have a pair of genes that do

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problems. Talk to your doctor or diagnostic testing should be done in


genetic counselor about testing your addition to newborn screening.
other children for CPT-1A deficiency.
During pregnancy, women carrying
CPT-1A deficiency carriers fetuses with CPT-1A may be at
Brothers and sisters who are not increased risk to develop serious
affected with CPT-1A deficiency still medical problems. Some women
have a chance to be carriers like their carrying fetuses with Fatty Acid
parents. Except in special cases, carrier Oxidation Disorders have developed:
testing should only be done in people
excessive vomiting
over 18 years of age.
abdominal pain
Each of the parents brothers and high blood pressure
sisters has a 50% chance to be a CPT- jaundice
1A deficiency carrier. It is important for abnormal fat storage in the liver
other family members to be told that severe bleeding
they could be carriers. There is a very
All women with a family history of
small chance they are also at risk to
CPT-1A should share this information
have children with CPT-1A deficiency.
with their obstetricians and other
Some states do not offer newborn health care providers before and during
screening for CPT-1A deficiency. any future pregnancies. Knowing about
However, expanded newborn screening these risks allows better medical care
through private laboratories is and early treatment if needed.
available for babies born in states that
Can other family members be tested?
do not screen for this condition.

Diagnostic testing for CPT-1A


When both parents are carriers,
deficiency
newborn screening results are not
To make sure they do not have the
adequate to rule out CPT-1A deficiency
condition, brothers and sisters of a
in a newborn baby. In this case, special

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child with CPT-1a deficiency can have also more common among the Native
special tests done on a skin sample. American Inuit people of Canada and
DNA testing may also be done if both Alaska. CPT-1A deficiency is rare in
mutations have been identified in the other ethnic groups around the world.
affected sibling.; The actual incidence is unknown.

Carrier testing for CPT-1A deficiency Does CPT-1A deficiency happen


Carrier testing may be available to more frequently in a certain ethnic
other family members. Ask your group?
metabolic doctor or genetic counselor CPT-1A deficiency can be seen in
about carrier testing for family every ethnic group and geographical
members. area. However, it is more common in
the North American Hutterite
Where can Confirmatory Testing be
community and also among the Native
done for this condition?
American Inuit people of Canada and
The confirmatory test for the diagnosis
Alaska.
is done by Liquid Chromatography
Mass Spectrometry (LC/MS) using Does CPT-1A deficiency go by any
blood sample. other names?

Center CPT-1A deficiency is sometimes also


PreventiNe Lifecare Pvt. Ltd. called:
RPT House, Plot No. 6, Sector 24,
CPT-1 deficiency
Turbhe, Navi Mumbai 400705
CPT-1 deficiency (liver)
Ph: 022-61980000/11

There is another type of CPT deficiency


How many people have CPT-1A
called CPT-1B, or muscle type. CPT-
deficiency?
1B is not discussed in this fact sheet.
CPT-1A deficiency is found in about
one in every 1200 babies in the North Where can I find more information?
American Hutterite community. It is

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Fatty Oxidation Disorders (FOD)


Family Support Group
http://www.fodsupport.org

Organic Acidemia Association


http://www.oaanews.org

United Mitochondrial Disease


Foundation
http://www.umdf.org

Children Living with Inherited


Metabolic Diseases (CLIMB)
http://www.climb.org.uk

Genetic Alliance
http://www.geneticalliance.org

Mito Action
http://www.mitoaction.org

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C
Can other family members be
arnitine

tested?
Palmitoyl Where can Confirmatory Testing
be done for this condition?
Transferase What is the cost of the
confirmatory test?
Deficiency, type 2
How many people have CPT-2
deficiency?
Disorder Name: Carnitine palmitoyl
transferase deficiency, type 2 Does CPT-2 deficiency happen
more often in a certain ethnic
Acronym: CPT-2 deficiency
group?
What is CPT-2 deficiency? Does CPT-2 deficiency go by any
What causes CPT-2 deficiency? other names?
If CPT-2 deficiency is not treated, Where can I find more
what problems occur? information?
What is the treatment for CPT-2
deficiency? This fact sheet contains general
What happens when CPT-2 information about CPT-2 deficiency.

deficiency is treated? Every child is different and some of this


How is CPT-2 deficiency information may not apply to your child
inherited? specifically. Not all is known about
What causes the CPT-2 enzyme to CPT-2 deficiency and, at present, there
be absent or not working is no standard treatment plan. Certain

correctly? treatments may be recommended for


Is there genetic testing available? some children but not others. Children
What other testing is available? with CPT-2 deficiency should be
Can you test during pregnancy? followed by a metabolic doctor in
Can other members of the family addition to their primary doctor.

have CPT-2 deficiency or be


What is CPT-2 deficiency?
carriers?

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Fatty Acid Oxidation Disorders: have problems breaking down fat into
energy for the body.
Fatty acid oxidation disorders
(FAODs) are a group of rare inherited
What causes CPT-2 deficiency?
conditions. They are caused by
CPT-2 deficiency occurs when an
enzymes that do not work properly.
enzyme, called carnitine palmitoyl
transferase type 2 (CPT-2), is either
A number of enzymes are needed to
break down fats in the body (a missing or not working properly. This

process called fatty acid oxidation). enzymes job is to help change certain

Problems with any of these enzymes fats in the food we eat into energy. It
also helps us use fat already stored in
can cause a fatty acid oxidation
the body.
disorder. People with FAODs cannot
properly break down fat from either
the food they eat or from fat stored in
their bodies.

The symptoms and treatment vary


between different FAODs. They can
also vary from person to person with
the same FAOD. See the fact sheets
for each specific FAOD.

FAODs are inherited in an autosomal


recessive manner and affect both
males and females.

CPT-2 deficiency stands for carnitine


palmitoyl transferase deficiency type Energy from fat keeps us going

2. It is one type of fatty acid oxidation whenever our bodies run low of their

disorder. People with CPT-2 deficiency main source of energy, a type of sugar

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called glucose. Our bodies rely on fat crisis. Some of the first signs of a
when we dont eat for a stretch of time metabolic crisis are:
like when we miss a meal or when we extreme sleepiness
sleep. behavior changes
irritable mood
When the normal enzyme is missing or
poor appetite
not working, the body cannot use fat
for energy, and must rely solely on Other symptoms then follow:
glucose. Although glucose is a good fever
source of energy, there is a limited diarrhea
amount available. Once the glucose vomiting
has been used up, the body tries to use hypoglycemia
fat without success. This leads to low
If a metabolic crisis is not treated, a
blood sugar, called hypoglycemia, and
child with CPT-2 deficiency can
to the build up of harmful substances
develop:
in the blood.
breathing problems
If CPT-2 deficiency is not treated, seizures
what problems occur? coma, sometimes leading to
A small number of babies with CPT-2 death
deficiency show symptoms shortly
CPT-2 deficiency in newborns
after birth. Others dont start showing
Rarely, a baby with CPT-deficiency
the effects until later in infancy. Most
shows symptoms in the newborn
people do not have symptoms until
period. Newborns with symptoms
their teen years or early adulthood.
usually have many episodes of
This is called the classic form of
metabolic crisis. Other health effects in
CPT-2 deficiency.
newborns can be:
Babies and children who show early
enlarged heart with irregular
signs of CPT-2 deficiency have
heartbeat
episodes of illness called metabolic

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enlarged liver Symptoms of metabolic crisis in babies


muscle weakness and children with CPT-2 deficiency
often happen after having nothing to
Some babies are also born with:
eat for more than a few hours.
kidney cysts
Symptoms are also more likely when a
cataracts
baby or child with CPT-2 deficiency
defects of the brain
gets sick or has an infection.

Without treatment, babies who have


Some children with CPT-2 deficiency
symptoms in the newborn period
have never had a metabolic crisis or
usually die very early in life.
other related health problems and are
only found to be affected after a brother
CPT-2 deficiency in infants and
or sister has been diagnosed.
children
A small number of children with CPT-2
CPT-2 deficiency in adults
deficiency start showing symptoms in
Most people with CPT-2 deficiency
late infancy or early childhood. If
have the adult form. This is also called
untreated, some of the effects can be:
classic CPT-2 deficiency, or the
muscle form.
repeated metabolic crises
learning problems Symptoms of classic CPT-2 deficiency
delays in walking and other usually start between 15 and 30 years
motor skills of age. Periods of muscle weakness are
liver problems common. Breakdown of muscle fibers
muscle weakness can happen. Symptoms usually happen
enlarged heart and irregular during heavy exercise or after going
heartbeat without food for a long period of time.
kidney problems Signs of muscle breakdown include:
muscle aches
Without treatment, many children with
muscle weakness
CPT-2 deficiency die early in life.
cramps

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reddish-brown color to the urine your child needs to be fed. In general,


it is often suggested that infants be fed
Adults who are not treated can develop
every four to six hours. Some babies
kidney failure.
need to eat even more frequently than
this. It is important that infants be fed
Classic CPT-2 deficiency does not
during the night. They may need to be
cause metabolic crises or heart
woken up to eat if they do not wake up
problems.
on their own. Your metabolic doctor
What is the treatment for CPT-2 and dietician will give you an
deficiency? appropriate feeding plan for your
Your baby's primary doctor will work infant. Your doctor will also give you a
with a metabolic doctor to care for your sick day plan tailored to your childs
child. Your doctor may also suggest needs for you to follow during illnesses
that you meet with a dietician familiar or other times when your child will not
with CPT-2 deficiency. eat.

Certain treatments may be advised for Your metabolic doctor will continue to
some children but not others. When advise you on how often your child
necessary, treatment is usually needed should eat as he or she gets older.
throughout life. The following are When they are well, many teens and
treatments sometimes recommended adults with CPT-2 deficiency can go
for babies and children with CPT-2 without food for up to 12 hours without
deficiency: problems. The other treatments usually
need to be continued throughout life.
1. Avoid going a long time without
food 2.Diet
Infants and young children with CPT-2 Sometimes a low fat, high
deficiency need to eat frequently to carbohydrate food plan is
prevent a metabolic crisis. Your recommended. Carbohydrates give the
metabolic doctor will tell you how often body many types of sugar that can be

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used as energy. In fact, for children Some children and adults may be
needing this treatment, most food in helped by taking L-carnitine. This is a
the diet should be carbohydrates safe and natural substance that helps
(bread, pasta, fruit, vegetables, etc.) body cells make energy. It also helps
and protein (lean meat and low-fat the body get rid of harmful wastes.
dairy foods). Any diet changes should Your doctor will decide whether or not
be made under the guidance of an your child needs L-carnitine. Unless
experienced dietician. you are advised otherwise, use only L-
carnitine prescribed by your doctor. Do
Children with CPT-2 deficiency cannot
not use any supplements without
use certain building blocks of fat called
checking with your doctor.
"long chain fatty acids". Your dietician
can help create a food plan low in these 4. Call your doctor at the start of any
fats. Much of the rest of the fat in the illness
diet will likely be in the form of medium Always call your health care provider
chain fatty acids. right away when your child has any of
the following:
Ask your doctor whether your child
needs to have any changes in his or her poor appetite
diet. low energy or excessive
sleepiness
3. MCT oil and L-carnitine
vomiting
Medium Chain Triglyceride oil (MCT
diarrhea
oil) is often used as part of the food
an infection
plan for people with CPT-2 deficiency.
a fever
This special oil has medium chain fatty
persistent muscle pain,
acids that can be used in small
weakness, or reddish-brown
amounts for energy. Your metabolic
color to the urine
doctor or dietician can guide you in
how to use this supplement. Babies and children with CPT-2
deficiency need to eat extra starchy

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food and drink more fluids during any drink fluids right away
illness - even if they may not feel eat something starchy or sugary
hungry or they could have a get to a hospital for treatment
metabolic crisis. Children who are sick
To help prevent muscle symptoms:
often dont want to eat. If they wont or
avoid prolonged or heavy
cant eat, they may need to be treated
exercise
in the hospital to prevent a metabolic
keep the body warm
crisis. Ask your metabolic doctor if
eat starchy or sugary food before
you should carry a special travel letter
and during periods of moderate
with medical instructions for your
exercise
childs care.

What happens when CPT-2


5. Avoid long periods of exercise
deficiency is treated?
and avoid getting cold
Treatment can help prevent or control
Long periods of strenuous exercise can
symptoms in some children with CPT-2
trigger symptoms in both children and
deficiency. Children who are treated
adults. So can cold weather. Muscle
early may be able to live healthy lives
effects can include:
with typical growth and development.
muscle aches Some children do continue to have
cramps episodes of metabolic crisis and other
weakness health problems despite treatment.
reddish-brown urine
When treated, adults with the classic
If muscle symptoms occur, prompt form of CPT-2 deficiency are expected
treatment is needed to prevent kidney to live healthy lives.
damage. Children or adults with
What causes the CPT-2 enzyme to be
muscle symptoms should:
absent or not working correctly?

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Genes tell the body to make various of the disease. However in a small
enzymes. People with CPT-2 deficiency number of cases, carriers of CPT-2
have a pair of genes that do not work have been reported with symptoms of
correctly. Because of the changes in the disorder.
this pair of genes, the CPT-2 enzyme
When both parents are carriers, there
either does not work properly or is not
is a 25% chance in each pregnancy for
made at all.
the child to have CPT-2 deficiency.
How is CPT-2 deficiency inherited? There is a 50% chance for the child to
be a carrier, just like the parents. And,
CPT-2 deficiency is inherited in an
there is a 25% chance for the child to
autosomal recessive manner. It affects
inherit two working genes.
both boys and girls equally.
Genetic counseling is available to
Everyone has a pair of genes that make
families who have children with CPT-2
the CPT-2 enzyme. In children with
CPT-2 deficiency, neither of these
genes works correctly. These children
inherit one non-working gene for the
condition from each parent.

Parents of children with CPT-2


deficiency are rarely affected with the
disorder. Instead, each parent has a
single recessive gene for CPT-2
deficiency. They are called carriers for
CPT-2 deficiency. Carriers do not have
CPT-2 deficiency because the other
gene of this pair is working correctly.
In most cases, carriers of CPT-2
deficiency do not have any symptoms

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deficiency. Genetic counselors can counselor if you have questions about


answer your questions about how CPT- testing for CPT-2 deficiency.
2 deficiency is inherited, choices
Can you test during pregnancy?
during future pregnancies, and how to
If both gene changes have been found
test other family members. Ask your
in your child with CPT-2 deficiency,
doctor about a referral to a genetic
DNA testing can be done during future
counselor.
pregnancies. The sample needed for
Is there genetic testing available? this test is obtained by either CVS or
Genetic testing for CPT-2 deficiency amniocentesis.
can be done on a blood sample.
If DNA testing would not be helpful, an
Genetic testing, also called DNA
enzyme test can be done on cells from
testing, looks for changes in the pair of
the fetus. Again, the sample needed for
genes that cause CPT-2 deficiency. In
this test is obtained by either CVS or
some children, both gene changes can
amniocentesis.
be found. However, in other children,
neither or only one of the two gene Parents may either choose to have
changes can be found, even though we
testing during pregnancy or wait until
know they are present.
birth to have the baby tested. A genetic
counselor can talk with you about your
DNA testing is not necessary to
choices and answer questions about
diagnose your child. It can be helpful
prenatal testing or testing your baby
for carrier testing or prenatal diagnosis,
after birth.
discussed below.

Can other members of the family


have CPT-2 deficiency or be carriers?
What other testing is available?
Having CPT-2 deficiency
CPT-2 deficiency can also be confirmed
The brothers and sisters of a baby with
by an enzyme test on a skin sample.
CPT-2 deficiency have a chance of
Talk to your doctor or your genetic

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being affected, even if they havent had Some states do not offer newborn
symptoms. Finding out whether other screening for CPT-2 deficiency.
children in the family have CPT-2 However, expanded newborn screening
deficiency is important because early through private labs is available for
treatment may prevent serious health babies born in states that do not screen
problems. Talk with your doctor or for this condition.
genetic counselor about testing your
When both parents are carriers,
other children for CPT-2 deficiency.
newborn screening results are not
CPT-2 deficiency carriers sufficient to rule out CPT-2 deficiency
Brothers and sisters who do not have in a newborn baby. In this case, special
CPT-2 deficiency still have a chance to diagnostic testing should be done in
be carriers like their parents. Except in addition to newborn screening.
special cases, carrier testing should
During pregnancy, women carrying
only be done in people over 18 years of
fetuses with CPT-2 deficiency may be
age.
at increased risk to develop serious
Each of the parents brothers and medical problems. Some women
sisters has a 50% chance to be a CPT-2 carrying fetuses with Fatty Acid
deficiency carrier. It is important for Oxidation Disorders have developed:
other family members to be told that
excessive vomiting
they could be carriers. There is a very
abdominal pain
small chance they are also at risk to
high blood pressure
have children with CPT-2 deficiency.
jaundice
Most commonly, carriers of CPT-2
abnormal fat storage in the liver
deficiency do not have any symptoms
severe bleeding
of the disease. However a small
number of carriers of CPT-2 have been
All women with a family history of
reported to have symptoms of the
CPT-2 deficiency should share this
disorder. information with their obstetricians and

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other health care providers before and Mass Spectrometry (LC/MS) using
during any future pregnancies. blood sample.
Knowing about these risks allows
Center
better medical care and early treatment
PreventiNe Lifecare Pvt. Ltd.
if needed.
RPT House, Plot No. 6, Sector 24,
Can other family members be tested? Turbhe, Navi Mumbai 400705
Ph: 022-61980000/11
Diagnostic Testing
Brothers and sisters of an affected How many people have CPT-2
child can be tested for CPT-2 deficiency?
deficiency using either a DNA test or a CPT-2 deficiency is rare. The actual
special enzyme test. incidence is unknown.

Carrier Testing Does CPT-2 deficiency happen more


If both gene changes have been found often in a certain ethnic group?
in the child with CPT-2 deficiency, CPT-2 deficiency does not happen
other family members can have DNA more often in any specific race, ethnic
testing to see if they are carriers. group, geographical area or country.

If DNA testing would not be helpful, Does CPT-2 deficiency go by any


other methods of carrier testing may be other names?
available. Your metabolic doctor or CPT-2 deficiency is also called:
genetic counselor can answer your
CPT-II deficiency
questions about carrier testing.
Carnitine palmyitoyltransferase
Where can Confirmatory Testing be II deficiency
done for this condition?
Where can I find more information?
The confirmatory test for the diagnosis
is done by Liquid Chromatography

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Fatty Oxidation Disorders (FOD) What causes the enzyme to be


Family Support Group absent or not working correctly?
http://www.fodsupport.org How is GA-2 inherited?
Is genetic testing available?
Organic Acidemia Association
What other testing is available?
http://www.oaanews.org
Can you test during pregnancy?
Can other members of the family
United Mitochondrial Disease
have GA-2 or be carriers?
Foundation
Can other family members be
http://www.umdf.org
tested?
Genetic Alliance Where can Confirmatory Testing
http://www.geneticalliance.org be done for this condition?
What is the cost of the
Mito Action
confirmatory test?
http://www.mitoaction.org
How many people have GA-2?

G
Does GA-2 happen more often in a
lutaric certain ethnic group?

acidemia, type 2 Does GA-2 go by any other


names?
Where can I find more
Disorder name: Glutaric acidemia,
type 2 information?

Acronym: GA-2
This fact sheet contains general
What is GA-2? information about GA-2. Every child is
What causes GA-2? different and some of these facts may
If GA-2 is not treated, what not apply to your child specifically.
problems occur? Certain treatments may be
What is the treatment for GA-2? recommended for some children but
What happens when GA-2 is not others. All children with GA-2
treated? should be followed by a metabolic

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doctor.
Organic Acid Disorders:
What is GA-2?
Organic acid disorders (OAs) are a
GA-2 stands for glutaric acidemia,
group of rare inherited conditions.
type 2. People with GA-2 have
They are caused by enzymes that do
problems breaking down fat and
not work properly. A number of
protein into energy for the body. GA-2
enzymes are needed to process
has symptoms that are part of two
protein from the food we eat for use by
different groups of disorders: fatty acid
the body. Problems with one or more
oxidation disorders and organic acid
of these enzymes can cause an
disorders.
organic acid disorder.

People with organic acid disorders


cannot break down protein properly.
This causes harmful substances to
build up in their blood and urine.
These substances can affect health,
growth and learning.

The symptoms and treatment vary


between different organic acid
disorders. They can also vary from
person to person with the same
organic acid disorder. See the fact
sheets for each specific organic acid
disorder.

Organic acid disorders are inherited


in an autosomal recessive manner
and affect both males and females.

doctor in addition to their primary


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What causes GA-2? Energy from fat and protein keeps us


GA-2 occurs when one of two different going whenever our body runs low of
enzymes is either missing or not its main source of energy, a type of
working properly. The enzymes sugar called glucose. Our bodies rely
responsible for GA-2 are called mainly on fat when we dont eat for a
electron transfer flavoprotein (ETF) stretch of time like when we miss a
and ETF-ubiquinone oxidoreductase
(ETF:QO). The job of these enzymes is Fatty Acid Oxidation Disorders:
to help make energy for the body by
Fatty acid oxidation disorders
breaking down certain fats and
(FAODs) are a group of rare inherited
proteins from the food we eat. They
conditions. They are caused by
also break down fat and protein already
enzymes that do not work properly.
stored in the body.

A number of enzymes are needed to


break down fats in the body (a
process called fatty acid oxidation).
Problems with any of these enzymes
can cause a fatty acid oxidation
disorder. People with FAODs cannot
properly break down fat from either
the food they eat or from fat stored in
their bodies.

The symptoms and treatment vary


between different FAODs. They can
also vary from person to person with
the same FAOD. See the fact sheets for
each specific FAOD.

FAODs are inherited in an autosomal


recessive manner and affect both
135 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY
males and females.
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BABYSHIELD TMS FACT SHEET

meal or when we sleep. hypoglycemia


increased levels of acidic
When either one of these two enzymes
substances in the blood, called
is missing, the body cannot break
metabolic acidosis
down protein and fat for energy, and
must rely on glucose. While glucose is If a metabolic crisis is not treated, a
a good source of energy, there is a child with GA-2 can develop:
limited amount available. Once the breathing problems
glucose has been used up, the body seizures
tries to use fat and protein with limited coma, sometimes leading to
success. This leads to the buildup of death
glutaric acid and other harmful
Symptoms can first show up in the
substances in the blood. It also causes
newborn period or later in childhood or
low blood sugar, called hypoglycemia.
sometimes even adulthood.
If GA-2 is not treated, what problems
GA-2 in newborns
occur?
Some babies have their first symptoms
GA-2 can cause bouts of illness called
shortly after birth. Rapid breathing and
metabolic crises. Some of the first
weak muscle tone often happen one to
symptoms of a metabolic crisis are:
two days after birth. Episodes of
extreme sleepiness
metabolic crisis often show up at this
behavior changes
time, too.
irritable mood
muscle weakness
Many babies with GA-2 have an odor
poor appetite that smells like sweaty feet. In
addition, they often have serious heart
Other symptoms then follow:
and liver problems.
fever
nausea Without treatment, most babies die
diarrhea within the first few weeks of life. Even
vomiting

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with treatment, many babies with GA-2 after going too long without
die of severe heart problems within a food
few months. during illness or infection

Some newborns with GA-2 also have Episodes of metabolic crisis can
birth defects. If this is the case, happen for the same reasons.
treatment is usually not helpful. Babies
Other symptoms of GA-2 happen in
with GA-2 and birth defects usually die
some people:
within the first weeks of life.
liver problems
GA-2 in childhood heart problems
The symptoms of GA-2 can be very low levels of carnitine, a
different from person to person. If substance that helps the body
symptoms do not happen in the use fat for energy
newborn period, they may begin involuntary movements
anytime from early childhood through
Some people with GA-2 never have
adulthood.
symptoms and are only found to be
Symptoms in childhood can include: affected after a brother or sister is
nausea diagnosed.
vomiting
What is the treatment for GA-2?
muscle weakness
Your childs primary doctor will work
periods of hypoglycemia
with a metabolic doctor and dietician
full metabolic crisis (described
familiar with GA-2 to provide your
above)
child with medical care.
Hypoglycemia can cause a child to feel
Certain treatments may be advised for
weak, shaky or dizzy with clammy, cold
some children but not others. When
skin. Hypoglycemia can occur:
necessary, treatment is usually needed
after strenuous exercise
throughout life. The following are
after eating too much protein

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treatments often recommended for for up to 12 hours without problems.


children with GA-2: They may need to continue the other
treatments throughout life.
1. Avoid going a long time without
food 2.Diet
Infants and young children with GA-2 A low-fat, low-protein, high-
need to eat frequently to prevent carbohydrate diet is often advised.
hypoglycemia or a metabolic crisis. Carbohydrates give the body many
Your metabolic doctor will tell you how types of sugar that can be used as
often your child needs to be fed. In energy. In fact, for children needing
general, it is often suggested that this treatment, most food in the diet
infants be fed every four to six hours. should be carbohydrates (bread, cereal,
Some babies need to eat even more pasta, fruit, vegetables, etc.). Do not
frequently than this. It is important that remove all fat and protein from the diet.
infants be fed during the night. They Children with GA-2 need a certain
may need to be woken up to eat if they amount of each to grow properly.
do not wake up on their own. Your
Your dietician can help you create a
metabolic doctor and dietician will give
food plan that meets your childs
you an appropriate feeding plan for
needs. Any diet changes should be
your infant. Your doctor will also give
made under the guidance of a dietician
you a sick day plan, tailored to your
experienced with GA-2.
childs needs, for you to follow during
illnesses or other times when your
2. Riboflavin, L-carnitine and
child will not eat.
glycine supplements

Your metabolic doctor will continue to Some children and adults with GA-2
advise you on how often your child
are helped by taking daily riboflavin
should eat as he or she gets older.
supplements. Check with your doctor
When they are well, many teens and
to see whether your child should take
adults with GA-2 can go without food riboflavin.

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Some children may be helped by taking During illness or infection, children


L-carnitine. This is a safe and natural with GA-2 have a much higher chance
substance that helps body cells make of developing hypoglycemia or a
energy. It also helps the body get rid of metabolic crisis. They need to drink
harmful wastes. Your doctor will fluids and eat extra carbohydrates
decide whether or not your child needs when they are ill even if they arent
L-carnitine supplements. Unless you hungry or they could have a
are advised otherwise, use only L- metabolic crisis.
carnitine prescribed by your doctor.
Children who are sick often dont want
Some people with GA-2 are helped by to eat. If they cant eat, or if they show
taking glycine supplements. Ask your signs of hypoglycemia or a metabolic
doctor whether your child should take crisis, they may need to be treated in
glycine. the hospital. Ask your metabolic
doctor if you should carry a special
Do not use any of these supplements
travel letter with medical instructions
without checking with your doctor.
for your childs care.

3. Call your doctor at the start of any


What happens when GA-2 is treated?
illness
Always call your health care provider GA-2 in newborns
when your child has any of the A small number of newborns with
following: symptoms of GA-2 have shown benefit
from treatment. But, in most cases,
poor appetite
treatment has not been helpful. Many
low energy or extreme
newborns with GA-2 die from heart
sleepiness
problems within the first few months of
vomiting
life.
diarrhea
an infection GA-2 in children
a fever

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With prompt and careful treatment, non-working gene for the condition
children and adults with GA-2 usually from each parent.
live healthy lives with normal growth
Parents of children with GA-2 rarely
and development.
have the disorder. Instead, each parent
The goal of treatment is to prevent has a single non-working gene for GA-
long-term problems. However, children 2. They are called carriers. Carriers do
who have repeated metabolic crises not have GA-2 deficiency because the
may develop life-long learning other gene of this pair is working
problems. correctly.

What causes the enzyme to be absent When both parents are carriers, there
or not working correctly? is a 25% chance in each pregnancy for
Genes tell the body to make various the child to have GA-2. There is a 50%
enzymes. People with GA-2 have a pair chance for the child to be a carrier, just
of genes that do not work correctly. like the parents. And, there is a 25%
Because of the gene changes, one of chance for the child to have two
the necessary enzymes does not work working genes.
properly or is not made at all.

How is GA-2 inherited?


GA-2 is inherited in an autosomal
recessive manner. It affects both boys
and girls equally.

Everyone has one pair of genes that


make the ETF enzyme and another pair
that makes the ETF:QO enzyme. In
children with GA-2, the pair of genes
for one of these enzymes does not work
correctly. These children inherit one

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changes in the pair of genes that cause


GA-2. Talk with your genetic counselor
or metabolic doctor if you have
questions about DNA testing.

DNA testing is not necessary to


diagnose your child. However, it can be
helpful for carrier or prenatal testing,
discussed below.

What other testing is available?


GA-2 can be confirmed by tests done
on urine, blood or skin samples. Ask
your metabolic doctor or genetic
counselor about testing for GA-2.

Can you test during pregnancy?


If both gene changes have been found
Genetic counseling is available to
in your child, DNA testing can be done
families who have children with GA-2.
during future pregnancies. The sample
Genetic counselors can answer your
needed for this test is obtained by
questions about how the condition is
either CVS or amniocentesis.
inherited, choices during future
pregnancies, and how to test other If DNA testing would not be helpful, an
family members. Ask your doctor about enzyme test can be done on cells from
a referral to a genetic counselor. the fetus. The sample needed for this
test is obtained by amniocentesis.
Is genetic testing available?
Genetic testing for GA-2 can be done Parents may choose to have testing
on a blood sample. Genetic testing, during pregnancy or wait until birth to
also called DNA testing, looks for the have the baby tested. A genetic

141 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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counselor can talk to you about your carriers. There is a small chance they
choices and answer questions about are also at risk to have children with
prenatal testing or testing your baby GA-2.
after birth.
Some states do not provide newborn
Can other members of the family screening for GA-2. However,
have GA-2 or be carriers? expanded newborn screening through
private labs is available for babies born
Having GA-2
in states that do not screen for this
The brothers and sisters of a baby with
condition.
GA-2 have a chance of being affected,
even if they havent shown symptoms. When both parents are carriers,
Finding out if other children in the newborn screening results are not
family have GA-2 is important because sufficient to rule out GA-2 in a newborn
early treatment may prevent serious baby. In this case, special diagnostic
health problems. Talk to your testing should be done in addition to
metabolic doctor or genetic counselor newborn screening.
about testing your other children for
Can other family members be tested?
GA-2.
Diagnostic testing
GA-2 carriers GA-2 can be confirmed by special tests
Brothers and sisters who do not have using urine, blood, or skin samples.
GA-2 still have a chance to be carriers
Carrier testing
like their parents. Except in special
Carrier testing for GA-2 may be
cases, carrier testing should only be
available. Ask your genetic counselor
done in people over 18 years of age.
or metabolic doctor whether carrier
Each of the parents brothers and testing is possible for your family.
sisters has a 50% chance to be a GA-2
Where can Confirmatory Testing be
carrier. It is important for other family
done for this condition?
members to be told that they could be

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The confirmatory test for the diagnosis Does GA-2 happen more often in a
is done by Gas Chromatography Mass certain ethnic group?
Spectrometry (GC/MS) using urine
GA-2 does not happen more often in
sample or by Mutations analysis from
any specific race, ethnic group,
whole blood, skin fibroblast or
geographical area or country.
lymphocytes of patient for 3 different
genes, ETFA, ETFB and ETFDH. Does GA-2 go by any other names?
GA-2 is sometimes also called:
Center
PreventiNe Lifecare Pvt. Ltd. glutaric acidemia-II
RPT House, Plot No. 6, Sector 24, glutaric aciduria-II
Turbhe, Navi Mumbai 400705 multiple acyl-CoA
Ph: 022-61980000/11
dehydrogenase deficiency

Academic Medical Center (MADD)

Laboratory Genetic Metabolic Diseases electron transfer flavoprotein

(F0-132) dehydrogenase deficiency

Meibergdreef 9 ETF/ETF QO deficiency

1105 AZ Amsterdam
Where can I find more information?
The Netherlands
Ph: +31 20 5662026 / 5393 Fatty Oxidation Disorders (FOD)
E-mail: gmz_enzym@amc.nl Family Support Group
http://www.fodsupport.org
What is the cost of the confirmatory
test? Organic Acidemia Association
http://www.oaanews.org
350 (+ 100 for fibroblast culturing)

United Mitochondrial Disease


How many people have GA-2?
Foundation
GA-2 is very rare. The actual incidence
http://www.umdf.org
is unknown.

143 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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CLIMB (Children Living with Inherited


Metabolic Disorders)
http://www.climb.org.uk

Genetic Alliance
http://www.geneticalliance.org/

PacNoRGG pamphlet: Glutaric


Acidemia Type II
http://www.westernstatesgenetics.org/
pacnorgg/PDFs_all-
081409/glut_acid_eng.pdf

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L
Can other family members be
ong chain 3-

tested?
hydroxyacyl-CoA Where can Confirmatory Testing
be done for this condition?
dehydrogenase What is the cost of the
confirmatory test?
deficiency
How many people have
LCHADD?
Disorder name: Long chain 3-
Does LCHADD happen more often
hydroxyacyl-CoA dehydrogenase
in a certain ethnic group?
deficiency
Does LCHADD go by any other
Acronym: LCHADD
names?
What is LCHADD? Where can I find more
What causes LCHADD? information?
If LCHADD is not treated, what
This fact sheet contains general
problems occur?
information about LCHADD. Every
What is the treatment for
child is different and some of this
LCHADD?
information may not apply to your child
What happens when LCHADD is
specifically. Certain treatments may be
treated?
recommended for some children but
What causes the LCHAD enzyme
not others. Children with LCHADD
to be absent or not working
should be followed by a metabolic
correctly?
doctor in addition to their primary
How is LCHADD inherited?
doctor.
Is there genetic testing available?
What other testing is available?
What is LCHADD?
Can you test during pregnancy?
LCHADD stands for long chain 3-
Can other members of the family
hydroxyacyl-CoA dehydrogenase
have LCHADD or be carriers?
deficiency. It is one type of fatty acid

145 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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LCHADD occurs when an enzyme,


Fatty Acid Oxidation Disorders:
called long chain 3-hydroxyacyl-CoA
Fatty acid oxidation disorders dehydrogenase (LCHAD), is either
(FAODs) are a group of rare inherited missing or not working properly. This
conditions. They are caused by enzymes job is to break down certain
enzymes that do not work properly. fats from the food we eat into energy. It
also breaks down fat already stored in
A number of enzymes are needed to
the body.
break down fats in the body (a
process called fatty acid oxidation).
Problems with any of these enzymes
can cause a fatty acid oxidation
disorder. People with FAODs cannot
properly break down fat from either
the food they eat or from fat stored in
their bodies.

The symptoms and treatment vary


between different FAODs. They can
also vary from person to person with
the same FAOD. See the fact sheets
for each specific FAOD.

FAODs are inherited in an autosomal


recessive manner and affect both
Energy from fat keeps us going
males and females.
whenever our bodies run low of their
oxidation disorder. People with main source of energy, a type of sugar
LCHADD have problems breaking called glucose. Our bodies rely on fat
down fat into energy for the body. when we dont eat for a stretch of time

What causes LCHADD?

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like when we miss a meal or when we irritability or jitteriness


sleep. behavior changes

When the normal LCHAD enzyme is If hypoglycemia is not treated, a child


missing or not working well, the body with LCHADD can develop:
cannot break down fat for energy. breathing problems
Instead, it must rely solely on glucose. swelling of the brain
Although glucose is a good source of seizures
energy, there is a limited amount coma, sometimes leading to
available. Once the glucose has been death
used up, the body tries to use fat
Symptoms often happen after having
without success. This leads to low
nothing to eat for more than a few
blood sugar, called hypoglycemia, and
hours. Symptoms are also more likely
to the build up of harmful substances
to occur when a person with LCHADD
in the blood.
gets sick or has an infection.
If LCHADD is not treated, what
Between episodes of hypoglycemia,
problems occur?
people with LCHADD are usually
LCHADD can cause mild effects in
healthy. However, repeated episodes
some people and more serious health
can cause brain damage. This can
problems in others. Babies and
result in learning disabilities or mental
children with LCHADD usually begin
retardation.
to show symptoms sometime from birth
through age two. LCHADD causes
Babies and children who are not
episodes of hypoglycemia. The first treated may have:
symptoms of hypoglycemia are: poor weight gain
delays in learning
extreme sleepiness or fatigue
delays in walking and other
weakness
motor skills
nausea
vomiting

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enlarged liver and other liver 1. Avoid going a long time without
problems food
enlarged heart and other heart Infants and young children with
problems LCHADD need to eat frequently to
vision loss due to build-up of prevent a metabolic crisis. Your
pigment in the retina metabolic doctor will tell you how often
anemia your child needs to be fed. In general,
nerve problems it is often suggested that infants be fed
bouts of muscle weakness and every four to six hours. Some babies
pain, especially after heavy need to eat even more frequently than
exercise or illness this. It is important that infants be fed
during the night. They may need to be
Some children with LCHADD have
woken up to eat if they do not wake up
never had symptoms and are only
on their own. Your metabolic doctor
found to be affected after a brother or
and dietician will give you an
sister is diagnosed.
appropriate feeding plan for your
infant. Your doctor will also give you a
What is the treatment for LCHADD?
sick day plan tailored to your childs
Your baby's primary doctor will work
needs for you to follow during illnesses
with a metabolic doctor to care for your
or other times when your child will not
child. Your doctor may also suggest
eat.
that you meet with a dietician familiar
with LCHADD.
Your metabolic doctor will continue to
advise you on how often your child
Certain treatments may be advised for
should eat as he or she gets older.
some children but not others. When
When they are well, many teens and
necessary, treatment is usually needed
adults with LCHADD can go without
throughout life. The following are
food for up to 12 hours without
treatments often recommended for
problems. The other treatments usually
children with LCHADD:
need to be continued throughout life.

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2.Diet acids can be used in small amounts for


Sometimes a low fat, high energy. Your metabolic doctor or
carbohydrate food plan is dietician can guide you in how to use
recommended. Carbohydrates give the this supplement. You will need to get a
body many types of sugar that can be prescription from your doctor to get
used as energy. In fact, for children MCT oil.
needing this treatment, most food in
Some children may be helped by L-
the diet should be carbohydrates
carnitine. This is a safe and natural
(bread, pasta, fruit, vegetables, etc.)
substance that helps body cells make
and protein (lean meat and low-fat
energy. It also helps the body get rid of
dairy foods). Any diet changes should
harmful wastes. Your doctor will
be made under the guidance of a
decide whether your child needs L-
dietician familiar with LCHADD.
carnitine. Unless you are advised
People with LCHADD cannot use otherwise, use only L-carnitine
certain building blocks of fat called prescribed by your doctor.
"long chain fatty acids". Your dietician
In addition to the above supplements,
can help create a food plan low in these
some doctors suggest taking DHA
fats. Much of the rest of the fat in the
(docosahexanoic acid) which may help
diet will likely be in the form of medium
prevent loss of eyesight. Ask your
chain fatty acids.
doctor whether your child should use
Ask your doctor if your child needs to this supplement.
have any changes in his or her diet.
Do not use any supplements or
3. MCT oil, L-carnitine and other medications without checking with
supplements your doctor.
Medium Chain Triglyceride oil (MCT
4. Call your doctor at the start of any
oil) is often used as part of the food
illness
plan for people with LCHADD. This
Always call your health care provider
special oil has medium chain fatty

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when your child has any of the Long periods of heavy exercise can
following: also trigger symptoms. Effects of
exercise may include:
poor appetite
muscle aches
low energy or excessive
cramps
sleepiness
weakness
vomiting
reddish-brown color to the urine
diarrhea
(caused by breakdown of muscle
an infection
fibers)
a fever
persistent muscle pain or If muscle symptoms occur, prompt
weakness, or reddish-brown treatment is needed to prevent kidney
color to the urine damage. Children or adults with
muscle symptoms should:
Children with LCHADD need to eat
drink fluids right away
extra starchy food and drink more
eat something starchy or sugary
fluids during any illness - even if they
get to a hospital for treatment
may not feel hungry or they could
develop hypoglycemia. Children who To help prevent muscle symptoms:
are sick often dont want to eat. If they avoid prolonged or heavy
wont or cant eat, children with exercise
LCHADD may need to be treated in the keep the body warm
hospital to prevent problems. eat carbohydrates before and
during periods of moderate
Ask your metabolic doctor if you
exercise
should carry a special travel letter with
medical instructions for your childs What happens when LCHADD is
care. treated?
With prompt and careful treatment,
5. Avoid prolonged exercise or
children with LCHADD can often live
exertion.

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healthy lives with typical growth and non-working gene for the condition
development. from each parent.

Even with treatment, some people with Parents of children with LCHADD are
LCHADD continue to have episodes of rarely affected with the disorder.
hypoglycemia. This can lead to Instead, each parent has a single non-
learning problems or mental working gene for LCHADD. They are
retardation. And, even with treatment, called carriers. Carriers do not have
some people still develop vision, LCHADD because the other gene of
muscle, liver or heart problems. this pair is working correctly.

What causes the LCHAD enzyme to When both parents are carriers, there
be absent or not working properly? is a 25% chance in each pregnancy for
Genes tell the body to make various the child to have LCHADD. There is a
enzymes. People with LCHADD have a 50% chance for the child to be a carrier,
pair of genes that do not work just like the parents. And, there is a
correctly. Because of the changes in 25% chance for the child to have two
this pair of genes, the LCHAD enzyme working genes.
either does not work properly or is not
made at all.

How is LCHADD inherited?


LCHADD is inherited in an autosomal
recessive manner. It affects both boys
and girls equally.

Everyone has a pair of genes that make


the LCHAD enzyme. In children with
LCHADD, neither of these genes works
correctly. These children inherit one

151 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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children with LCHADD have one


particular change in both genes of this
pair.

DNA testing is not necessary to


diagnose your child. It can be helpful
for carrier testing or prenatal diagnosis,
discussed below.

What other testing is available?


LCHADD can also be confirmed by a
special test called a "fatty acid
oxidation probe" using a skin sample.
Talk to your doctor or your genetic
counselor if you have questions about
testing for LCHADD.
Genetic counseling is available to
families who have children with Can you test during pregnancy?
LCHADD. Genetic counselors can If both gene changes have been found
answer your questions about how in your child with LCHADD, DNA
LCHADD is inherited, choices during testing can be done during future
future pregnancies, and how to test pregnancies. The sample needed for
other family members. Ask your doctor this test is obtained by either CVS or
about a referral to a genetic counselor. amniocentesis.

Is genetic testing available? If DNA testing would not be helpful,


Genetic testing for LCHADD can be testing during pregnancy can be done
done on a blood sample. Genetic by a special test called a "fatty acid
testing, also called DNA testing, looks oxidation probe" using cells from the
for changes in the pair of genes that fetus. Again, the sample needed for this
causes LCHADD. About 70% of

152 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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test is obtained by either CVS or special cases, carrier testing should


amniocentesis. only be done in people over 18 years of
age.
Parents may either choose to have
testing during pregnancy or wait until Each of the parents brothers and
birth to have the baby tested. A genetic sisters has a 50% chance to be an
counselor can talk to you about your LCHADD carrier. It is important for
choices and answer questions about other family members to be told that
prenatal testing or testing your baby they could be carriers. There is a small
after birth. chance they are also at risk to have
children with LCHADD.
Can other members of the family
have LCHADD or be carriers? All states offer newborn screening for
Having LCHADD LCHADD. However, when both parents
are carriers, newborn screening results
The brothers and sisters of a baby with
are not sufficient to rule out LCHADD
LCHADD have a chance of being
in a newborn baby. In this case, special
affected, even if they havent had
diagnostic testing should be done in
symptoms. Finding out whether other
addition to newborn screening.
children in the family have LCHADD is
important because early treatment may During pregnancy, women carrying
prevent serious health problems. Talk fetuses with LCHADD are at risk to
to your doctor or genetic counselor develop serious medical problems.
about testing your other children for Some of these women develop:
LCHADD.
excessive vomiting
LCHADD Carriers abdominal pain
high blood pressure
Brothers and sisters who do not have
jaundice
LCHADD still have a chance to be
abnormal fat storage in the liver
carriers like their parents. Except in
severe bleeding

153 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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All women with a family history of Ph: 022-61980000/11


LCHADD should share this information
How many people have LCHADD?
with their obstetricians and other
health care providers before and during
LCHADD is a rare disorder. The actual
any future pregnancies. Knowing about
incidence is unknown.
these risks allows early treatment.
Does LCHADD happen more often in
Can other family members be tested?
a certain ethnic group?

Diagnostic testing Although LCHADD happens in every


Brothers and sisters can be tested for ethnic group, it happens more often in
LCHADD by DNA testing or other
people who have ancestors from
special tests.
Finland.

Carrier testing Does LCHADD go by any other


If both gene changes have been found
names?
in the child with LCHADD, other family
members can have DNA testing to see LCHADD is also called:
if they are carriers.
LCHAD deficiency
Where can Confirmatory Testing be 3hydroxyacyl-CoA
dehydrogenase, long chain,
done for this condition? deficiency
Trifunctional protein deficiency,
The confirmatory test for the diagnosis type 1
is done by Liquid Chromatography
A variant of LCHADD is called
Mass Spectrometry (LC/MS) using
Trifunctional Protein Deficiency (TFP).
blood sample.
Please see the TFP fact sheet for
Center information on this condition.

PreventiNe Lifecare Pvt. Ltd.


Where can I find more information?
RPT House, Plot No. 6, Sector 24,
Turbhe, Navi Mumbai 400705

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Fatty Oxidation Disorders (FOD) Family


Support Group
http://www.fodsupport.org
Organic Acidemia Association
http://www.oaanews.org
United Mitochondrial Disease Foundation
http://www.umdf.org
Genetic Alliance
http://www.geneticalliance.org
Mito Action
http://www.mitoaction.org

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M
Where can Confirmatory Testing
edium chain

be done for this condition?


acyl-CoA What is the cost of the
confirmatory test?
dehydrogenase How many people have MCADD?
Does MCADD happen more often
deficiency

in a certain ethnic group?


Does MCADD go by any other
Disorder Name: Medium chain acyl-
names?
CoA dehydrogenase deficiency
Where can I find more
Acronym: MCADD
information?
What is MCADD?
This fact sheet contains general
What causes MCADD?
information about MCADD. Every child
If MCADD is not treated, what
is different and some of this
problems occur?
information may not apply to your child
What is the treatment for
specifically. Certain treatments may be
MCADD?
recommended for some children but
What happens when MCADD is
not others. Children with MCADD
treated?
should be followed by a metabolic
What causes the MCAD enzyme
doctor in addition to their primary
to be absent or not working
doctor.
correctly?
How is MCADD inherited?
What is MCADD?
Is genetic testing available?
MCADD stands for medium chain
What other testing is available?
acyl-CoA dehydrogenase deficiency. It
Can you test during pregnancy?
is one type of fatty acid oxidation
Can other members of the family
disorder. People with MCADD have
have MCADD or be carriers?
problems breaking down fat into
Can other family members be
energy for the body.
tested?

156 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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Fatty Acid Oxidation Disorders: missing or not working properly. This


enzymes job is to break down certain
Fatty acid oxidation disorders fats in the food we eat into energy. It
(FAODs) are a group of rare inherited also breaks down fat already stored in
conditions. They are caused by the body.
enzymes that do not work properly.

A number of enzymes are needed to


break down fats in the body (a
process called fatty acid oxidation).
Problems with any of these enzymes
can cause a fatty acid oxidation
disorder. People with FAODs cannot
properly break down fat from either
the food they eat or from fat stored in
their bodies.

The symptoms and treatment vary


between different FAODs. They can
also vary from person to person with
the same FAOD. See the fact sheets
for each specific FAOD.
Energy from fat keeps us going
whenever our bodies run low of their
FAODs are inherited in an autosomal
main source of energy, a type of sugar
recessive manner and affect both
called glucose. Our bodies rely on fat
males and females.
when we dont eat for a stretch of time
like when we miss a meal or when we
What causes MCADD?
sleep.
MCADD occurs when an enzyme,
called medium chain acyl-CoA
When the MCADD enzyme is missing
dehydrogenase (MCAD), is either
or not working well, the body cannot

157 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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use certain types of fat for energy, and If a metabolic crisis is not treated, a
must rely solely on glucose. Although child with MCADD can develop:
glucose is a good source of energy, breathing problems
there is a limited amount available. seizures
Once the glucose has been used up, the coma, sometimes leading to
body tries to use fat without success. death
This leads to low blood sugar, called
Between episodes of metabolic crisis,
hypoglycemia, and to the buildup of
people with MCADD are usually
harmful substances in the blood.
healthy. However, repeated episodes
If MCADD is not treated, what can cause permanent brain damage.
problems occur? This may result in learning problems,
MCADD can cause bouts of illness mental retardation or spasticity.
called metabolic crises. Children with
Symptoms often happen after having
MCADD often show effects for the first
nothing to eat for more than a few
time between three months and three
hours.
years of age. Some of the first
Hypoglycemia can occur, with or
symptoms of a metabolic crisis are:
without other symptoms of metabolic
extreme sleepiness crisis, just by going too long without
behavior changes food. Hypoglycemia can cause a person
irritable mood to feel weak, shaky, or dizzy, and to
poor appetite have clammy, cold skin. If not treated,
hypoglycemia can lead to coma and
Some of these other symptoms may
even death.
also follow:
fever Hypoglycemia and metabolic crises are
diarrhea also more likely to occur when a person
vomiting with MCADD gets sick or has an
hypoglycemia infection.

158 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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Some children with MCADD have very to eat if they do not wake up on their
mild symptoms or no symptoms at all. own. Your metabolic doctor and
dietician will give you an appropriate
feeding plan for your infant. Your
What is the treatment for MCADD?
doctor will also give you a sick day
Your babys primary doctor will work
plan, tailored to your childs needs, for
with a metabolic doctor to care for your
you to follow during illnesses or other
child. Your doctor may also suggest
times when your child will not eat.
that you meet with a dietician familiar
with MCADD. Your metabolic doctor will continue to
advise you on how often your child
Certain treatments may be advised for
should eat as he or she gets older.
some children but not others. When
When they are well, many teens and
necessary, treatment is usually needed
adults with MCADD can go without
throughout life. The following are
food for up to 12 hours without
treatments often recommended for
problems. Most children do not have
children with MCADD:
metabolic crises past the age of ten.
However, some may need to continue
1. Avoid going a long time without
treatment throughout life.
food
Infants and young children with
2.Diet
MCADD need to eat frequently to
Sometimes a low fat, high
prevent hypoglycemia or a metabolic
carbohydrate food plan is
crisis. Your metabolic doctor will tell
recommended. Carbohydrates give the
you how often your child needs to be
body many types of sugar that can be
fed. In general, it is often suggested
used as energy. In fact, for children
that infants be fed every four to six
needing this treatment, most food in
hours. Some babies need to eat even
the diet should be carbohydrates
more frequently than this. It is
(bread, pasta, fruit, vegetables, etc.)
important that infants be fed during the
and protein (lean meat and low-fat
night. They may need to be woken up

159 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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dairy foods). Your dietician can create 2. low energy or excessive


a food plan with the correct type and sleepiness
amount of fat your child needs. Any 3. vomiting
diet changes should be made under the 4. diarrhea
guidance of an experienced dietician. 5. an infection
6. a fever
Ask your doctor whether or not your
child needs to have any changes in his Children with MCADD need to eat
or her diet. extra starchy food and drink more
fluids during any illness - even if they
3. L-carnitine
may not feel hungry or they could
Some children may be helped by taking
develop hypoglycemia or a metabolic
L-carnitine. This is a safe and natural
crisis. Children who are sick often
substance that helps body cells make
dont want to eat. If they wont or cant
energy. It also helps the body get rid of
eat, they may need to be treated in the
harmful wastes.
hospital to prevent problems.

Your doctor will decide whether or not Ask your metabolic doctor if you
your child needs L-carnitine. Unless should carry a special travel letter with
you are advised otherwise, use only L- medical instructions for your childs
carnitine prescribed by your doctor. Do care.
not use any medications without
What happens when MCADD is
checking with your doctor.
treated?
4. Call your doctor at the start of any
With prompt and careful treatment,
illness
children with MCADD usually live
Always call your health care provider
healthy lives with typical growth and
when your child has any of the
development. The goal of treatment is
following:
to prevent long-term problems.
1. poor appetite
However, children who have repeated

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metabolic crises may have life-long the other gene of this pair is working
learning disabilities, spasticity, chronic correctly. When both parents are
muscle weakness or other effects. carriers, there is a 25% chance in each
pregnancy for the child to have
What causes the MCAD enzyme to be
MCADD. There is a 50% chance for the
absent or not working correctly?
child to be a carrier, just like the
Genes tell the body to make various
parents. And, there is a 25% chance for
enzymes. People with MCADD have a
the child to have two working genes.
pair of genes that do not work
correctly. Because of the changes in
this pair of genes, the MCAD enzyme
either does not work properly or is not
made at all.

How is MCADD inherited?


MCADD is inherited in an autosomal
recessive manner. It affects both boys
and girls equally.

Everyone has a pair of genes that make


the MCAD enzyme. In children with
MCADD, neither of these genes works
correctly. These children inherit one
non-working gene for the condition
from each parent.

Genetic counseling is available to


Parents of children with MCADD rarely
families who have children with
have the disorder. Instead, each parent
MCAD. Genetic counselors can answer
has a single non-working gene for
your questions about how MCADD is
MCADD. They are called carriers.
inherited, choices during future
Carriers do not have MCADD because

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pregnancies, and how to test other If both gene changes have been found
family members. Ask your doctor about in your child with MCADD, DNA
a referral to a genetic counselor. testing can be done during future
pregnancies. The sample needed for
Is genetic testing available?
this test is obtained by either CVS or
Genetic testing for MCADD can be
amniocentesis.
done on a blood sample. Genetic
testing, also called DNA testing, looks If DNA testing would not be helpful, an
for changes in the pair of genes that enzyme test can be done during
cause MCADD. In many children with pregnancy on cells from the fetus.
MCADD, both gene changes can be Again, the sample needed for this test
found. However, in other children, only is obtained by either CVS or
one or neither of the two gene changes amniocentesis.
can be found, even though we know
Parents may either choose to have
they are present.
testing during pregnancy or wait until
DNA testing is not necessary to birth to have the baby tested. A genetic
diagnose your child. It can be helpful counselor can talk to you about your
for carrier testing or prenatal diagnosis, choices and answer questions about
discussed below. prenatal testing or testing your baby
after birth.
What other testing is available?
MCADD can also be confirmed either Can other members of the family
by a blood test called an acylcarnitine have MCADD or be carriers?
profile or an enzyme test on a skin Having MCADD
sample. Talk to your doctor or your
The brothers and sisters of a baby with
genetic counselor if you have questions
MCADD have a chance of being
about testing for MCADD.
affected, even if they have had no
Can you test during pregnancy? symptoms. Finding out whether other
children in the family have MCADD is

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important because early treatment may During pregnancy, women carrying


prevent serious health problems. Talk fetuses with MCADD may be at
to your doctor or genetic counselor increased risk to develop serious
about testing your other children for medical problems. Some women
MCADD. carrying fetuses with Fatty Acid
Oxidation Disorders have developed:
MCADD Carriers
Brothers and sisters who do not have excessive vomiting
MCADD still have a chance to be abdominal pain
carriers like their parents. Except in high blood pressure
special cases, carrier testing should jaundice
only be done on people over 18 years of abnormal fat storage in the liver
age. severe bleeding

Each of the parents brothers and All women with a family history of
sisters has a 50% chance to be an MCADD should share this information
MCADD carrier. It is important for with their obstetricians and other
other family members to be told that health care providers before and during
they could be carriers. There is a small any future pregnancies. Knowing about
chance they are also at risk to have these risks allows better medical care
children with MCADD. and early treatment if needed.

All states offer newborn screening for Can other family members be tested?
MCADD. However, when both parents
Diagnostic testing
are carriers, newborn screening results
Brothers and sisters can be tested for
are not sufficient to rule out MCADD in
MCADD using DNA testing or other
a newborn baby. In this case, special
special tests.
diagnostic testing should be done in
addition to newborn screening. Carrier Testing
If both gene changes have been found

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in your child with MCADD, other The Netherlands


family members can have DNA testing Ph: +31 20 5662026 / 5393
to see if they are carriers. E-mail: gmz_enzym@amc.nl

If DNA testing would not be helpful, What is the cost of the confirmatory
carrier testing can also be done by an test?
enzyme test on a skin sample. 350 (+ 100 for fibroblast culturing)

Where can Confirmatory Testing be How many people have MCADD?


done for this condition? About one in every 15,000 babies in the
The confirmatory test for the diagnosis United States is born with MCADD.
is done by Gas Chromatography Mass
Does MCADD happen more often in a
Spectrometry (GC/MS) using urine
certain ethnic group?
sample or by estimation of Medium or
MCADD happens more often in white
Short chain 3-hydroxyacyl-CoA
people from Northern Europe and the
dehydrogenase enzyme activity in
United States. About 1 in every 70
patient fibroblasts and primary marker
Caucasians is a carrier for MCADD.
is identified in octanonyl Carnitines
(C8) in TMS.

Center
Does MCADD go by any other
PreventiNe Lifecare Pvt. Ltd.
names?
RPT House, Plot No. 6, Sector 24,
Turbhe, Navi Mumbai 400705 MCADD is also sometimes called:

Ph: 022-61980000/11
MCAD deficiency
Academic Medical Center ACADM deficiency
Laboratory Genetic Metabolic MCADH deficiency
Diseases (F0-132)
Meibergdreef 9 Where can I find more information?

1105 AZ Amsterdam

164 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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Fatty Oxidation Disorders (FOD)


Family Support Group
http://www.fodsupport.org

Organic Acidemia Association


http://www.oaanews.org

United Mitochondrial Disease


Foundation
http://www.umdf.org

Genetic Alliance
http://www.geneticalliance.org

PacNoRGG pamphlet: MCAD


http://www.westernstatesgenetics.org/
pacnorgg_page.htm

Genetic Metabolic Dietitians


International
http://www.gmdi.org/index.php?option
=com_content&view=article&id=42:mca
d&catid=7:resources

Mito Action
http://www.mitoaction.org

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S
Where can Confirmatory Testing
hort chain acyl-

be done for this condition?


CoA What is the cost of the
confirmatory test?
dehydrogenase How many people have SCADD?
Does SCADD happen more often
deficiency

in a certain ethnic group?


Does SCADD go by any other
Disorder name: Short chain acyl-
CoA dehydrogenase deficiency names?
Where can I find more
Acronym: SCADD
information?
What is SCADD?
What causes SCADD? This fact sheet contains general

If SCADD is not treated, what information on SCADD. Every child

problems occur? with SCADD is different and some of

What is the treatment for this information may not apply to your

SCADD? child specifically. Not all is known

What happens when SCADD is about SCADD and, at present, there is

treated? no standard treatment plan. Certain

What causes the SCAD enzyme to treatments may be recommended for

be absent or not working some children but not others. Children

correctly? with SCADD should be followed by a

How is SCADD inherited? metabolic doctor in addition to their

Is genetic testing available? primary doctor.

What other testing is available?


What is SCADD?
Can you test during pregnancy?
SCADD stands for short chain acyl-
Can other members of the family
CoA dehydrogenase deficiency. It is
have SCADD or be carriers?
one type of fatty acid oxidation
Can other family members be
disorder. Some people with SCADD
tested?

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Fatty Acid Oxidation Disorders: What causes SCADD?

SCADD occurs when an enzyme, called


Fatty acid oxidation disorders
short chain acyl-CoA dehydrogenase
(FAODs) are a group of rare inherited
(SCAD) is either missing or not
conditions. They are caused by
working properly. This enzymes job is
enzymes that do not work properly.
to break down certain fats from the
A number of enzymes are needed to food we eat into energy. It also breaks
break down fats in the body (a down fat already stored in the body.
process called fatty acid oxidation).
Problems with any of these enzymes
can cause a fatty acid oxidation
disorder. People with FAODs cannot
properly break down fat from either
the food they eat or from fat stored in
their bodies.

The symptoms and treatment vary


between different FAODs. They can
also vary from person to person with
the same FAOD. See the fact sheets
for each specific FAOD.

FAODs are inherited in an autosomal


recessive manner and affect both Energy from fat keeps us going
males and females. whenever our bodies run low of their
main source of energy, a type of sugar
cannot break down fat into energy for
called glucose. Our bodies rely on fat
the body. However, most babies with
when we dont eat for a stretch of time
newborn screening results showing
SCADD never have symptoms.

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like when we miss a meal or when we SCADD in infants


sleep. This type of SCADD is found in
newborns and infants. Symptoms,
Some people with SCADD cannot
when they happen, often start between
properly break down fat for energy.
the first week and 3 months of life.
However, most people with SCADD do
not seem to have this problem and do Some of the first symptoms of a
not ever develop symptoms. metabolic crisis are:
extreme sleepiness
If SCADD is not treated, what
behavior changes
problems occur?
irritable mood
poor appetite
SCADD is a highly variable and not
well understood. Most babies found to
Other symptoms then follow:
have SCADD through newborn
fever
screening never have symptoms. In
diarrhea
fact, so far, there have been only about
vomiting
20 people with SCADD reported to
increased levels of acidic
have health effects. Things that cause
substances in the blood, called
stress, such as lack of sleep, going
metabolic acidosis
without food for too long, illness, or
infection are thought to trigger If a metabolic crisis is not treated, a
episodes of illness called metabolic child with SCADD can develop:
crisis in some children but not others. breathing problems
seizures
For the small number of people with
coma, sometimes leading to
SCADD who show effects, the
death
condition occurs in two different forms:
one found in infants, the other found in Other effects of SCADD seen in some
adults. infants and children:
poor weight gain

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delays in learning and shortness of breath. The muscle


delays in walking and other problems often get worse after heavy
motor skills exercise or exertion.
hyperactivity
What is the treatment for SCADD?
decreased or increased muscle
Your baby's primary doctor may work
tone
with a metabolic doctor to care for your
muscle weakness
child. Your doctor may also suggest
enlarged liver
that you meet with a dietician familiar
enlarged spleen
with SCADD.
Symptoms of a metabolic crisis often
Certain treatments may be advised for
happen after having nothing to eat for
some children but not others. Babies
more than a few hours. Symptoms are
found to have SCADD on newborn
also more likely when a child with
screening, but who have not shown
SCADD gets sick or has an infection.
any effects, may not need treatment.
Many children with this condition have When necessary, treatment is usually
never had any effects and may only be needed throughout life. The following
found to have SCADD after a brother or are treatments recommended for some,
sister has been diagnosed. Most but not all, children with SCADD:
children diagnosed through newborn
1. Avoid going a long time without
screening never develop any symptoms
food
related to SCADD.
Some babies and young children with
SCADD in adults SCADD may need to eat often to avoid
The second type of SCADD is found in a metabolic crisis. These children
adults. The adult form of SCADD should not go without food for more
affects just the muscles. It can cause than four to six hours. In fact, some
ongoing muscle problems, pain and babies may need to eat even more often
weakness. Adults with SCADD can than this. They may also need to be fed
also have episodes of nausea, vomiting during the night. Your metabolic doctor

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will tell you whether your child needs Ask your doctor whether or not your
to be fed more often than normal. If so, child needs to have any changes in his
you will receive an eating plan tailored or her diet.
to your childs specific needs.
3. L-Carnitine and Riboflavin
Your metabolic doctor will continue to Some children may be helped by taking
advise you on how often your child L-carnitine. This is a safe and natural
should eat as he or she gets older. substance that helps the body create
When they are well, most teens and energy. It also helps the body get rid of
adults with SCADD can go without harmful wastes. Your doctor will
food for up to 12 hours. People who decide whether or not your child needs
have had symptoms may need to L-carnitine. Unless you are advised
continue the other treatments otherwise, use only L-carnitine
throughout life. prescribed by your doctor. A few
children with SCADD have been helped
2.Diet
by riboflavin (vitamin B2) supplements.
A low fat, high carbohydrate food plan
Ask your metabolic doctor whether
may be advised for some children with
your child should take riboflavin.
SCADD. Carbohydrates give the body
many types of sugar that can be used Do not use any medications or
as energy. In fact, for children needing supplements without checking with
this treatment, most food in the diet your doctor.
should be carbohydrates (bread, pasta,
4. Call your doctor at the start of any
fruit, vegetables, etc.) and protein (lean
illness
meat and low-fat dairy foods). Any diet
Call your health care provider when
changes should be made under the
your child has any of the following:
guidance of a dietician familiar with
SCADD.
1. poor appetite
2. low energy or excessive
sleepiness

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3. vomiting learning delays, muscle weakness and


4. diarrhea other health problems despite
5. an infection treatment.
6. a fever
What causes the SCAD enzyme to be
7. persistent muscle pain or
absent or not working properly?
weakness
Genes tell the body to make various
Some children with SCADD may need enzymes. People with SCADD have a
to eat extra starchy food and drink pair of genes that do not work
more fluids during an illness even if correctly. Because of the changes in
they may not feel hungry to prevent a this pair of genes, the SCAD enzyme
metabolic crisis. Children who are sick may not work properly or may not be
often dont want to eat. If they wont or made at all. Only a small number of
cant eat, some children with SCADD babies found to have SCADD through
may need to be treated in the hospital newborn screening will actually have
to prevent problems. If needed, your symptoms.
doctor will give you a sick day plan
How is SCADD inherited?
for you to follow during illness or other
SCADD is inherited in an autosomal
times when your child will not eat
recessive manner. It affects both boys
What happens when SCADD is and girls equally.
treated?
Everyone has a pair of genes that make
It is not known how effective treatment
the SCAD enzyme. In children with
is in preventing problems. Treatment
SCADD, neither of these genes works
may help prevent or control symptoms
correctly. These children inherit one
in some children. Children who need
non-working gene for the condition
treatment and are treated early may be
from each parent.
able to live healthy lives with typical
growth and development. Some
Parents of children with SCADD rarely
children, though, may continue to have have the disorder. Instead, each parent

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has a single non-working gene for Genetic counseling is available to


SCADD. They are called carriers. families who have children with
Carriers do not have SCADD because SCADD. Genetic counselors can
the other gene of this pair is working answer your questions about how
correctly. SCADD is inherited, choices during
future pregnancies, and how to test
When both parents are carriers, there
other family members. Ask your doctor
is a 25% chance in each pregnancy for
about a referral to a genetic counselor.
the child to have SCADD. There is a
50% chance for the child to be a carrier, Is there genetic testing available?
just like the parents. And, there is a Genetic testing for SCADD can be done
25% chance for the child to have two on a blood sample. Genetic testing,
working genes. also called DNA testing, looks for
changes in the pair of genes that cause
SCADD. DNA testing is often used to
diagnose SCADD in children. In some
affected children, both gene changes
can be found. However, in other
children, neither or only one of the two
gene changes can be found, even
though we know they are present.

DNA testing results will not help


establish if your child will develop
symptoms from SCADD. However, it
can be helpful for carrier testing or
prenatal diagnosis, discussed below.
Talk with your metabolic doctor or
genetic counselor if you have questions
about DNA testing for SCADD.

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What other testing is available? Having SCADD


SCADD can be confirmed by an The brothers and sisters of an affected
enzyme test using a blood or skin baby have a chance of having SCADD,
sample. Talk to your doctor or your even if they havent had symptoms.
genetic counselor if you have questions Talk with your doctor or genetic
about testing for SCADD. counselor about testing your other
children for SCADD.
Can you test during pregnancy?
If both gene changes have been found SCADD Carriers
in your child with SCADD, DNA testing Brothers and sisters who do not have
can be done during future pregnancies. SCADD still have a chance to be
The sample needed for this test is carriers like their parents. Except in
obtained by either CVS or special cases, carrier testing should
amniocentesis. only be done in people over 18 years of
age.
If DNA testing would not be helpful,
testing during pregnancy can be Each of the parents brothers and
attempted by performing an enzyme sisters has a 50% chance to be an
test on fetal cells. Again, the sample SCADD carrier. It is important for other
needed for these tests is obtained by family members to be told that they
either CVS or amniocentesis. could be carriers. There is a small
chance they are also at risk to have
Parents may either choose to have
children with SCADD.
testing during pregnancy or wait until
birth. A genetic counselor can talk to Some states do not offer newborn
you about your choices and answer screening for SCADD. However,
other questions about prenatal testing expanded newborn screening is
or testing your baby after birth available through private labs for
babies born in states that do not screen
Can other members of the family
for this condition.
have SCADD or be carriers?

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When both parents are carriers, Diagnostic testing


newborn screening results are not Brothers and sisters can be tested for
sufficient to rule out SCADD in a SCADD using a blood or skin sample.
newborn baby. In this case, special
Carrier testing
diagnostic testing should be done in
If both gene changes have been found
addition to newborn screening.
in your child with SCADD, other family
During pregnancy, women carrying members can have DNA testing to see
fetuses with SCADD may be at if they are carriers.
increased risk to develop serious
If DNA testing would not be helpful,
medical problems. Some women
other methods of carrier testing may be
carrying fetuses with Fatty Acid
available. Your metabolic doctor or
Oxidation Disorders have developed:
genetic counselor can answer your
excessive vomiting questions about carrier testing.
abdominal pain
Where can Confirmatory Testing be
high blood pressure
done for this condition?
jaundice
The confirmatory test for the diagnosis
abnormal fat storage in the liver
is done by Gas Chromatography Mass
severe bleeding
Spectrometry (GC/MS) using urine
All women with a family history of sample or by estimation of Short chain
SCADD should share this information acyl- CoA dehydrogenase activity in
with their obstetricians and other patient fibroblasts.
health care providers before and during
Center
any future pregnancies. Knowing about
PreventiNe Lifecare Pvt. Ltd.
these risks allows better medical care
RPT House, Plot No. 6, Sector 24,
and early treatment if needed.
Turbhe, Navi Mumbai 400705
Can other family members be tested? Ph: 022-61980000/11

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Academic Medical Center ACADS deficiency


Laboratory Genetic Metabolic Diseases SCADH deficiency
(F0-132)
Where can I find more information?
Meibergdreef 9
1105 AZ Amsterdam
Fatty Oxidation Disorders (FOD)
The Netherlands Family Support Group
Ph: +31 20 5662026 / 5393 http://www.fodsupport.org
E-mail: gmz_enzym@amc.nl
Organic Acidemia Association
What is the cost of the confirmatory http://www.oaanews.org
test?
United Mitochondrial Disease
350 (+ 100 for fibroblast culturing)
Foundation
http://www.umdf.org
How many people have SCADD?
SCADD was originally thought to be
Children Living with Inherited
very rare. However newborn screening
Metabolic Diseases (CLIMB)
for this disorder revealed that SCADD
http://www.climb.org.uk
is more common than previously
believed. The actual incidence is Genetic Alliance
unknown. http://www.geneticalliance.org

Does SCADD happen more frequently Mito Action


in a certain ethnic group? http://www.mitoaction.org
SCADD does not happen more often in
any specific race, ethnic group,
geographical area or country.

Does SCADD go by any other names?


SCADD is also sometimes called:

SCAD deficiency

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S
Can other family members be
hort Chain 3-

tested?
Hydroxyacyl-CoA Where can Confirmatory Testing
be done for this condition?
Dehydrogenase What is the cost of the
confirmatory test?
Deficiency
How many people have
Disorder Name: Short chain 3- M/SCHADD?
hydroxyacyl-CoA dehydrogenase Does M/SCHADD happen more
deficiency often in a certain ethnic group?
Acronym: M/SCHADD Does M/SCHADD go by any other
names?
What is M/SCHADD?
Where can I find more
What causes M/SCHADD?
information?
If M/SCHADD is not treated, what
problems occur? This fact sheet contains general
What is the treatment for information about M/SCHADD. Every
M/SCHADD? child is different and some of this
What happens when M/SCHADD information may not apply to your child
is treated? specifically. Very little is known about
What causes the SCHAD enzyme M/SCHADD and, at present, there is no
to be absent or not working standard treatment plan. Certain
correctly? treatments may be recommended for
How is M/SCHADD inherited? some children but not others. Children
Is there genetic testing available? with M/SCHADD should be followed
What other testing is available? by a metabolic doctor in addition to
Can you test during pregnancy? their primary doctor.
Can other members of the family
have M/SCHADD or be carriers? What is M/SCHADD?

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M/SCHADD stands for medium/short


between different FAODs. They can
chain 3-hydroxyacyl CoA
also vary from person to person with
dehydrogenase deficiency. This
the same FAOD. See the fact sheets
disorder is also known as 3-
for each specific FAOD.
hydroxyacyl CoA dehydrogenase
deficiency. It is one type of fatty acid FAODs are inherited in an autosomal
oxidation disorder. Some people with recessive manner and affect both
M/SCHADD have problems using fat males and females.
for energy. However, most babies with
newborn screening results showing What causes M/SCHADD?
M/SCHADD never have symptoms. M/SCHADD occurs when an enzyme,
called short chain 3-hydroxyacyl CoA
Fatty Acid Oxidation Disorders: dehydrogenase (SCHAD), is either
missing or not working properly. This
Fatty acid oxidation disorders
enzymes job is to help change certain
(FAODs) are a group of rare inherited
fats in the food we eat into energy for
conditions. They are caused by
the body. It also helps us use fat
enzymes that do not work properly.
already stored in the body.

A number of enzymes are needed to


break down fats in the body (a
process called fatty acid oxidation).
Problems with any of these enzymes
can cause a fatty acid oxidation
disorder. People with FAODs cannot
properly break down fat from either
the food they eat or from fat stored in
their bodies.

The symptoms and treatment vary

177 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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found to have M/SCHADD on newborn


screening do not seem to have this
problem and do not develop symptoms.

If M/SCHADD is not treated, what


problems occur?
M/SCHADD is highly variable and not
well understood. Things that cause
stress, such as lack of sleep, lack of
food, illness or infection are thought to
trigger episodes of illness called
metabolic crises in some children with
M/SCHADD but not in others.

Some of the first symptoms of a


metabolic crisis are:
extreme sleepiness
behavior changes
irritable mood
poor appetite

Energy from fat keeps us going Other symptoms then follow:


whenever our bodies run low of their fever
main source of energy, a type of sugar diarrhea
called glucose. Our bodies rely on fat
vomiting
when we don't eat for a stretch of time -
low blood sugar, called
like when we miss a meal or when we
hypoglycemia
sleep.
If a metabolic crisis is not treated, a
Some people with M/SCHADD cannot
child with M/SCHADD can develop:
break down fat for energy. Most babies breathing problems

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seizures Certain treatments may be advised for


swelling of the brain some children but not others. When
coma, sometimes leading to necessary, treatment is usually needed
death throughout life. The following are
treatments that may be recommended
Other effects of M/SCHADD can
for some children with M/SCHADD:
include:
1. Avoid going a long time without
irregular heart beat and other
food
heart problems
Some infants and young children with
enlarged heart
M/SCHADD may need to eat frequently
liver problems
to prevent a metabolic crisis. Your
muscle problems
metabolic doctor will tell you how often
high levels of insulin in the
your child needs to be fed. In general,
blood in some babies
it is often suggested that infants that
need to avoid fasting be fed every four
Symptoms of a metabolic crisis often
to six hours. Some babies may need to
happen after having nothing to eat for
eat even more frequently than this. It is
more than a few hours. Symptoms are
important that these infants be fed
also more likely when a person with
during the night. If needed, your
M/SCHADD gets sick or has an
metabolic doctor and dietician will give
infection.
you an appropriate feeding plan for
What is the treatment for your infant. Your doctor may also give
M/SCHADD? you a sick day plan tailored to your
Your babys primary doctor may work childs needs for you to follow during
with a metabolic doctor to care for your illnesses or other times when your
child. Your doctor may also suggest child will not eat.
that you meet with a dietician familiar
2.Diet
with M/SCHADD.
Sometimes a low fat, high
carbohydrate food plan is

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recommended. Carbohydrates give the Do not use any medications or


body many types of sugar that can be supplements without checking with
used as energy. In fact, for children your doctor.
needing this treatment, most food in
4. Call your doctor at the start of any
the diet should be carbohydrates
illness
(bread, pasta, fruit, vegetables, etc.)
If your child has shown previous
and protein (lean meat and low-fat
symptoms of M/SCHADD, always call
dairy foods). Any diet changes should
your health care provider when he or
be made under the guidance of a
she has any of the following:
dietician familiar with M/SCHADD.

1. poor appetite
Ask your doctor whether your child
2. low energy or excessive
needs to have any changes in his or her
sleepiness
diet.
3. vomiting
3. L-carnitine supplements and other 4. diarrhea
medications 5. an infection
Some children may be helped by taking 6. a fever
L-carnitine. This is a safe and natural 7. persistent muscle pain or
substance that helps the body create weakness
energy. It also helps the body get rid of
Children who have had symptoms of
harmful wastes. Your doctor will
M/SCHADD need to eat extra starchy
decide whether your child needs L-
food and drink more fluids during any
carnitine. Unless you are advised
illness - even if they may not feel
otherwise, use only L-carnitine
hungry - or they could develop a
prescribed by your doctor.
metabolic crisis. Children who are sick
Babies with high insulin levels may often dont want to eat. If they wont or
need medication. Your doctor will let cant eat, children with symptoms of
you know if your child needs to take M/SCHADD may need to be treated in
medication for this. the hospital to prevent problems.

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Ask your metabolic doctor if you either does not work properly or is not
should carry a special travel letter with made at all.
medical instructions for your childs
How is M/SCHADD inherited?
care.
M/SCHADD is inherited in an
What happens when M/SCHADD is autosomal recessive manner. It affects
treated? both boys and girls equally.
It is not known how effective treatment
Everyone has a pair of genes that make
is in preventing health problems. It is
the SCHAD enzyme. In children with
hoped that with prompt and careful
M/SCHADD, neither of these genes
treatment children with M/SCHADD
works correctly. These children inherit
will be able to live healthy lives with
one non-working gene for the condition
typical growth and development.
from each parent.
The goal of treatment is to prevent
Parents of children with M/SCHADD
death and serious health problems.
rarely have the disorder. Instead, each
However, children who have repeated
parent has a single non-working gene
episodes of hypoglycemia or metabolic
for M/SCHADD. They are called
crisis may develop brain damage. This
carriers. Carriers do not have
can result in learning disabilities,
M/SCHADD because the other gene of
mental retardation or other lifelong
this pair is working correctly.
effects.

When both parents are carriers, there


What causes the SCHAD enzyme to
is a 25% chance in each pregnancy for
be absent or not working correctly?
the child to have M/SCHADD. There is
Genes tell the body to make various
a 50% chance for the child to be a
enzymes. People with M/SCHADD
carrier, just like the parents. And, there
have a pair of genes that do not work
is a 25% chance for the child to have
correctly. Because of the changes in
two working genes.
this pair of genes, the SCHAD enzyme

181 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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pair of genes that cause M/SCHADD.


Ask your metabolic doctor or genetic
counselor about genetic testing for
M/SCHADD.

DNA testing is not necessary to


diagnose your child. It can be helpful
for carrier testing or prenatal diagnosis,
discussed below.

What other testing is available?

M/SCHADD can confirmed by a special


test called a fatty acid oxidation
probe using a skin sample. Talk to
your doctor or your genetic counselor if
you have questions about testing for
Genetic counseling is available to
M/SCHADD.
families who have children with
M/SCHADD. Genetic counselors can Can you test during pregnancy?
answer your questions about how
It may be possible to test for
M/SCHADD is inherited, choices
M/SCHADD during pregnancy either
during future pregnancies, and how to
by DNA testing or through a special
test other family members. Ask your
test called a fatty acid oxidation
doctor about a referral to a genetic
probe using cells from the fetus. The
counselor.
sample needed for these tests is
Is genetic testing available? obtained by either CVS or
amniocentesis.
Genetic testing for M/SCHADD may be
available. Genetic testing, also called Parents can either choose to having
DNA testing, look for changes in the testing during pregnancy or wait until

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birth to have the baby tested. A genetic Each of the parents brothers and
counselor can talk to you about your sisters has a 50% chance to be a
choices and answer other questions M/SCHADD carrier. It is important for
you may have about prenatal testing or other family members to be told that
testing your baby after birth. they could be carriers. There is a very
small chance they are also at risk to
Can other members of the family
have children with M/SCHADD.
have M/SCHADD or be carriers?
Some states do not offer newborn
Having M/SCHADD
screening for M/SCHADD. However,

The brothers and sisters of a baby with expanded newborn screening through
private labs is available for babies born
M/SCHADD have a small chance of
in states that do not screen for
having this condition, even if they
M/SCHADD.
havent had symptoms. Finding out
whether other children in the family
When both parents are M/SCHADD
have M/SCHADD may be important
carriers, newborn screening results are
because early treatment may prevent
not sufficient to rule out M/SCHADD in
serious health problems. Talk to your
a newborn baby. In this case, special
doctor or genetic counselor about
diagnostic testing should be done in
testing your other children for
addition to newborn screening.
M/SCHADD.

During pregnancy, women carrying


M/SCHADD Carriers
fetuses with M/SCHADD may be at
Brothers and sisters who do not have
increased risk to develop serious
M/SCHADD still have a chance to be
medical problems. Some women
carriers like their parents. Except in
carrying fetuses with Fatty Acid
special cases, carrier testing should
Oxidation Disorders have developed:
only be done in people over 18 years of
age.
excessive vomiting
abdominal pain

183 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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high blood pressure diagnosis is done by Gas


jaundice Chromatography Mass Spectrometry
abnormal fat storage in the liver (GC/MS) using urine sample or by
severe bleeding estimation of Medium or Short chain
3-hydroxyacyl-CoA dehydrogenase
All women with a family history of
enzyme activity in patient fibroblasts.
M/SCHADD should share this
information with their obstetricians and Center
other health care providers before and PreventiNe Lifecare Pvt. Ltd.

during any future pregnancies. RPT House, Plot No. 6, Sector 24,

Knowing about these risks allows Turbhe, Navi Mumbai 400705

better medical care and early treatment Ph: 022-61980000/11


if needed.
Academic Medical Center
Laboratory Genetic Metabolic Diseases
Can other family members be tested?
(F0-132)
Diagnostic testing Meibergdreef 9
Brothers and sisters can be tested for 1105 AZ Amsterdam
M/SCHADD using a skin sample. DNA The Netherlands
testing using a blood sample may be Ph: +31 20 5662026 / 5393
possible, too. E-mail: gmz_enzym@amc.nl

Carrier Testing What is the cost of the confirmatory


Carrier testing for M/SCHADD may be test?
available. Ask your metabolic doctor or 350 (+ 100 for fibroblast culturing)
genetic counseling whether carrier
testing is possible. How many people have M/SCHADD?
M/SCHADD is very rare. The actual
Where can Confirmatory Testing be incidence is unknown.
done for this condition?
Does M/SCHADD happen more
The confirmatory test for the frequently in a certain ethnic group?

184 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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M/SCHADD does not happen more Children Living with Inherited


often in any specific race, ethnic group, Metabolic Diseases (CLIMB)
geographical area or country. http://www.climb.org.uk

Does M/SCHADD go by any other Genetic Alliance


names? http://www.geneticalliance.org
M/SCHADD is sometimes also called:
Mito Action
SCHAD deficiency http://www.mitoaction.org
SCHADD
HADHSC deficiency
HADH deficiency
HAD deficiency
L-3-alpha-hydroxyacyl-CoA
dehydrogenase, short chain,
deficiency

Where can I find more information?

Fatty Oxidation Disorders (FOD)


Family Support Group
http://www.fodsupport.org

Organic Acidemia Association


http://www.oaanews.org

United Mitochondrial Disease


Foundation
http://www.umdf.org

185 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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What causes the TFP enzyme to


be absent or not working
correctly?
How is TFP deficiency inherited?
Is genetic testing available?
What other testing is available?
Can you test during pregnancy?
Can other members of the family
have TFP deficiency or be
carriers?

T
Can other family members be
rifunctional tested?
Where can Confirmatory Testing
protein be done for this condition?

deficiency What is the cost of the


confirmatory test?

Disorder name: Trifunctional protein How many people have TFP

deficiency deficiency?

Acronym: TFP deficiency Does TFP deficiency happen more


often in a certain ethnic group?
What is TFP deficiency? Does TFP deficiency go by any
What causes TFP deficiency? other names?
If TFP deficiency is not treated, Where can I find more
what problems occur? information?
What is the treatment for TFP
deficiency? This fact sheet contains general

What happens when TFP information about TFP deficiency.

deficiency is treated? Every child is different and some of this


information may not apply to your child
specifically. Not all is known about

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Fatty Acid Oxidation Disorders: by a metabolic doctor in addition to


their primary doctor.
Fatty acid oxidation disorders
(FAODs) are a group of rare inherited What is TFP deficiency?
conditions. They are caused by TFP deficiency stands for "trifunctional
enzymes that do not work properly. protein deficiency". It is one type of
fatty acid oxidation disorder. Some
A number of enzymes are needed to
people with TFP deficiency have
break down fats in the body (a
problems breaking down fat into
process called fatty acid oxidation).
energy for the body.
Problems with any of these enzymes
can cause a fatty acid oxidation
What causes TFP deficiency?
disorder. People with FAODs cannot
properly break down fat from either TFP deficiency occurs when a group of
the food they eat or from fat stored in enzymes, called trifunctional protein
their bodies. (TFP), is either missing or not working
properly. The job of TFP is to break
The symptoms and treatment vary
down certain fats from the food we eat
between different FAODs. They can
into energy. It also breaks down fat
also vary from person to person with
already stored in the body
the same FAOD. See the fact sheets
for each specific FAOD.

FAODs are inherited in an autosomal


recessive manner and affect both
males and females.

TFP deficiency and, at present, there is


no standard treatment plan. Certain
treatments may be recommended for
some children but not others. Children
with TFP deficiency should be followed

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amount available. Once the glucose


has been used up, the body tries to use
fat without success. This leads to low
blood sugar, called hypoglycemia, and
to the buildup of harmful substances in
the blood.

If TFP deficiency is not treated, what


problems occur?
TFP deficiency can cause mild
symptoms in some people or more
serious health problems in others.
There are three forms of TFP
deficiency: early, childhood and
mild.
Energy from fat keeps us going
whenever our bodies run low of their Babies and children with early and
main source of energy, a type of sugar childhood TFP deficiency can have
called glucose. Our bodies rely on fat episodes of illness called metabolic
when we don't eat for a stretch of time - crisis. Some of the first symptoms of a
like when we miss a meal or when we metabolic crisis are:
sleep. Our bodies rely on fat when we extreme sleepiness
dont eat for a stretch of time like behavior changes
when we miss a meal or when we irritable mood
sleep. muscle weakness
poor appetite
When TFP is missing or not working
well, the body cannot use fats for Some of these other symptoms may
energy. Instead, it must rely solely on also follow:
glucose. Although glucose is a good fever
source of energy, there is a limited nausea

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diarrhea during times of stress, such as


vomiting surgery
hypoglycemia
Early TFP deficiency
increased levels of acidic
substances in the blood, called
Babies with early TFP deficiency
metabolic acidosis usually show symptoms anywhere
from birth through age two. The first
If a metabolic crisis is not treated, a
symptoms are often:
child with TFP deficiency can develop:
breathing problems poor appetite
seizures sluggishness
coma, sometimes leading to extreme sleepiness
death
muscle weakness
absent reflexes
Periods of hypoglycemia can happen
no response to pain
without other symptoms of metabolic
delays in walking and learning
crisis. Hypoglycemia causes:
weakness
Babies with early TFP deficiency often
shakiness
have many episodes of metabolic
dizziness crisis.
clammy, cold skin
if untreated, coma, and Other effects of early TFP deficiency
sometimes death can include:
serious heart problems and
In children with TFP deficiency, either enlarged heart
hypoglycemia or a metabolic crisis can
build-up of fat in the liver and
happen:
other liver problems
after going too long without food
breathing problems
after long periods of exercise
during illness or infection Infants with early TFP who remain
untreated usually die of heart or

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breathing problems by three years of after going without food for a


age. long period of time

Childhood TFP deficiency Signs of muscle breakdown are:


muscle aches
Childhood TFP deficiency can cause
cramps
episodes of hypoglycemia and
weakness
metabolic crisis. Between these
reddish-brown color to the urine
episodes, children with TFP deficiency
breathing problems
are usually healthy. However, repeated
episodes may cause brain damage. If muscle symptoms are not treated,
This could result in learning problems kidney failure can occur.
or mental retardation.
The mild form of TFP deficiency does
Bouts of muscle weakness and pain not cause metabolic crises or heart or
happen in some children, especially liver problems.
after heavy exercise, stress or illness.
What is the treatment for TFP
Mild/muscle TFP deficiency deficiency?
Your baby's primary doctor will work
The mild form of TFP deficiency has
with a metabolic doctor and a dietician
been reported in a small number of
familiar with TFP deficiency to care for
people. Symptoms can begin anywhere
your child to care for your child.
from age two to adulthood.
Certain treatments may be advised for
Episodes of muscle weakness are
some children but not others. When
common. Breakdown of muscle fibers
necessary, treatment is usually needed
can occur. This usually happens:
throughout life. The following are
treatments that may be recommended
after strenuous exercise or
for children with TFP deficiency:
exertion
during illness or infection

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1. Avoid going a long time without 2.Diet


food A low fat, high carbohydrate food plan
Infants and young children with TFP is often recommended. Carbohydrates
deficiency need to eat frequently to give the body many types of sugar that
prevent hypoglycemia or a metabolic can be used as energy. In fact, for
crisis. Your metabolic doctor will tell children needing this treatment, most
you how often your child needs to be food in the diet should be
fed. In general, it is often suggested carbohydrates (bread, pasta, fruit,
that infants be fed every four to six vegetables, etc.) and protein (lean meat
hours. Some babies need to eat even and low-fat dairy foods). Any diet
more frequently than this. It is changes should be made under the
important that infants be fed during the guidance of an experienced dietician.
night. They may need to be woken up
People with TFP deficiency cannot use
to eat if they do not wake up on their
certain building blocks of fat called
own. Your metabolic doctor and
long chain fatty acids. Your dietician
dietician will give you an appropriate
can help create a food plan low in these
feeding plan for your infant. Your
fats. Much of the rest of the fat in the
doctor will also give you a sick day
diet will likely be in the form of medium
plan tailored to your childs needs for
chain fatty acids.
you to follow during illnesses or other
times when your child will not eat.
Ask your doctor if your child needs to
have any changes in his or her diet.
Your metabolic doctor will continue to
advise you on how often your child
3. MCT oil and L-carnitine
should eat as he or she gets older.
When they are well, many teens and Medium Chain Triglyceride oil (MCT
adults with TFP deficiency can go oil) is often used as part of the food
without food for up to 12 hours without plan for people with TFP deficiency.
problems. The other treatments usually This special oil has medium chain fatty
need to be continued throughout life. acids that can be used in small

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amounts for energy. Your metabolic a fever


doctor or dietician can tell you how to persistent muscle pain or
use this supplement. You will need to weakness
get a prescription from your doctor to reddish-brown color to the urine
get MCT oil.
Children with TFP deficiency need to
Some children may be helped by L- eat extra starchy food and drink more
carnitine. This is a safe and natural fluids during any illness - even if they
substance that helps body cells create may not feel hungry - or they could
energy. It also helps the body get rid of develop a metabolic crisis. Children
harmful wastes. Your doctor will who are sick often dont want to eat. If
decide whether your child needs L- they wont or cant eat, children with
carnitine. Unless you are advised TFP deficiency may need to be treated
otherwise, use only L-carnitine in the hospital to prevent hypoglycemia
prescribed by your doctor. or metabolic crisis. Ask your metabolic
doctor if you should carry a special
Do not use any medication or
travel letter with medical instructions
supplement without checking with your
for your childs care.
doctor.
5. Avoid heavy exercise and extreme
4. Call your doctor at the start of any
cold.
illness
Long periods of heavy exercise can
Always call your doctor when your
trigger symptoms in people with TFP
child has any of the following:
deficiency. Effects of exercise can
include muscle aches, cramps and
poor appetite
weakness. Muscle fibers may break
low energy or excessive
down. This can turn the urine a
sleepiness
reddish-brown color.
vomiting
diarrhea
If muscle symptoms occur, prompt
an infection
treatment is needed to prevent kidney

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damage. Children or adults with with treatment. This can cause


muscle symptoms should: permanent brain damage and may
result in learning disabilities or mental
drink fluids right away
retardation.
eat something starchy or sugary
Get to a hospital for treatment. Mild/muscle TFP deficiency
When treated, people with mild/muscle
To prevent muscle symptoms:
TFP deficiency usually remain healthy.
avoid prolonged or heavy
This form does not affect intelligence.
exercise
avoid extreme cold
eat starchy or sugary foods What causes the trifunctional protein
before and during periods of enzyme group to be absent or not
moderate exercise or exertion working properly?
Genes tell the body to make various
What happens when TFP deficiency
enzymes. People with TFP deficiency
is treated?
have a pair of genes that do not work
correctly. Because of the changes in
Early TFP deficiency
this pair of genes, the TFP enzymes
Most babies with early TFP deficiency
either do not work properly or are not
die of heart or breathing problems,
even when treated. However, treatment made at all.

may help prolong life in some babies.


How is TFP deficiency inherited?
TFP deficiency is inherited in an
Childhood TFP deficiency
autosomal recessive manner. It affects
With prompt and careful treatment,
both boys and girls equally.
children with TFP deficiency can often
live healthy lives with typical growth
Everyone has a pair of genes that make
and development. However, some
the TFP enzyme group. In children with
children continue to have episodes of
TFP deficiency, neither of these genes
hypoglycemia or metabolic crisis, even
works correctly. These children inherit

193 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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one non-working gene for the condition is a 25% chance for the child to have
from each parent. two working genes.

Parents of children with TFP deficiency Genetic counseling is available to


rarely have the disorder. Instead, each families who have children with TFP
parent has a single non-working gene deficiency. Genetic counselors can
for TFP deficiency. They are called answer your questions about how TFP
carriers. Carriers do not have TFP deficiency is inherited, choices during
future pregnancies, and how to test
other family members. Ask your doctor
about a referral to a genetic counselor.

Is genetic testing available?


Genetic testing for TFP deficiency can
be done on a blood sample. Genetic
testing, also called DNA testing, looks
for changes in the pair of genes that
cause TFP deficiency. In some affected
children, both gene changes can be
found. However, in other children,
neither or only one of the two gene
changes can be found, even though we
know they are present.
because the other gene of this pair is
working correctly. DNA testing is not necessary to
diagnose your child. It can be helpful
When both parents are carriers, there
for carrier testing or prenatal diagnosis,
is a 25% chance in each pregnancy for
discussed below. Ask your metabolic
the child to have TFP deficiency. There
doctor or genetic counselor if you have
is a 50% chance for the child to be a
questions about DNA testing for TFP
carrier, just like the parents. And, there
deficiency.

194 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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What other testing is available? Can other members of the family


TFP deficiency can be confirmed by have TFP deficiency or be carriers?
special enzyme tests using a skin or
Having TFP deficiency
muscle sample. Talk to your doctor or
The brothers and sisters of a baby with
your genetic counselor if you have
TFP deficiency have a chance of being
questions about testing for TFP
affected, even if they havent had
deficiency.
symptoms. Finding out whether other
Can you test during pregnancy? children in the family have TFP
If both gene changes have been found deficiency is important because early
in your child with TFP deficiency, DNA treatment may prevent serious health
testing can be done during future problems. Talk to your doctor or
pregnancies. The sample needed for genetic counselor about testing your
this test is obtained by either CVS or other children for TFP deficiency.
amniocentesis.
TFP deficiency carriers
If DNA testing would not be helpful, Brothers and sisters who do not have
special enzyme tests can be during TFP deficiency still have a chance to be
pregnancy using cells from the fetus. carriers like their parents. Except in
Again, the sample needed for this test special cases, carrier testing should
is obtained by either CVS or only be done in people over 18 years of
amniocentesis. age.

Parents may either choose to have Each of the parents brothers and
testing during pregnancy or wait until sisters has a 50% chance to be a TFP
birth to have the baby tested. A genetic deficiency carrier. It is important for
counselor can talk to you about your other family members to be told that
choices and answer questions about they could be carriers. There is a small
prenatal testing or testing your baby chance they are also at risk to have
after birth. children with TFP deficiency.

195 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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All states offer newborn screening for Diagnostic testing


TFP. However, when both parents are Brothers and sisters can be tested for
TFP deficiency carriers, newborn TFP deficiency by DNA testing or
screening results are not sufficient to special enzyme tests.
rule out TFP deficiency in a newborn
Carrier testing
baby. In this case, special diagnostic
If both gene changes have been found
testing should be done in addition to
in your child with TFP deficiency, other
newborn screening.
family members can have DNA testing
During pregnancy, women carrying to see if they are carriers.
fetuses with TFP deficiency are at risk
Where can Confirmatory Testing be
to develop serious medical problems.
done for this condition?
There is a small risk of:

Plasma acylcarnitine analysis will


excess vomiting
show a characteristic pattern of MTPD.
abdominal pain
The disorder may be required further
high blood pressure
biochemical and molecular genetic
jaundice
testing for confirmation.
severe bleeding
abnormal fat storage in the liver Center
PreventiNe Lifecare Pvt. Ltd.
All women with a family history of TFP
RPT House, Plot No. 6, Sector 24,
deficiency should share this
Turbhe, Navi Mumbai 400705
information with their obstetricians and
Ph: 022-61980000/11
other health care providers before and
during any future pregnancies. How many people have TFP
Knowing about these risks allows early deficiency?
treatment.
TFP deficiency is a very rare disorder.
Can other family members be tested? The actual incidence is unknown.

196 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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Does TFP deficiency happen more Genetic Alliance


often in a certain ethnic group? http://www.geneticalliance.org

TFP deficiency does not happen more Mito Action


often in any specific race, ethnic group, http://www.mitoaction.org
geographical area or county.

Does TFP deficiency go by any other


names?

TFP deficiency is sometimes also


called:

mitochondrial trifunctional
protein deficiency

Where can I find more information?

Fatty Oxidation Disorders (FOD)


Family Support Group
http://www.fodsupport.org

Organic Acidemia Association


http://www.oaanews.org

United Mitochondrial Disease


Foundation
http://www.umdf.org

197 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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V
Where can Confirmatory Testing
ery long chain

be done for this condition?


acyl-CoA What is the cost of the
confirmatory test?
dehydrogenase How many people have VLCADD?
Does VLCADD happen more often
Disorder Name: Very long chain acyl-
in a certain ethnic group?
CoA dehydrogenase
Does VLCADD go by any other
Acronym: VLCADD
names?
Where can I find more
What is VLCADD?
information?
What causes VLCADD?
If VLCADD is not treated, what
This fact sheet contains general
problems occur?
information about VLCADD. Every
What is the treatment for
child is different and some of this
VLCADD?
information may not apply to your child
What happens when VLCADD is
specifically. Certain treatments may be
treated?
recommended for some children but
What causes the VLCAD enzyme
not others. Children with VLCADD
to be absent or not working
should be followed by a metabolic
correctly?
doctor in addition to their primary
How is VLCADD inherited?
doctor.
Is genetic testing available?
What other testing is available? What is VLCADD?
Can you test during pregnancy? VLCADD stands for "very long chain
Can other members of the family acyl-CoA dehydrogenase deficiency". It
have VLCADD or be carriers? is one type of fatty acid oxidation
Can other family members be disorder. People with VLCADD have
tested? problems breaking down certain types
of fat into energy for the body.

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Fatty Acid Oxidation Disorders: missing or not working properly. This


enzyme's job is to break down certain
Fatty acid oxidation disorders fats from the food we eat into energy. It
(FAODs) are a group of rare inherited also breaks down fat already stored in
conditions. They are caused by the body.
enzymes that do not work properly.

A number of enzymes are needed to


break down fats in the body (a
process called fatty acid oxidation).
Problems with any of these enzymes
can cause a fatty acid oxidation
disorder. People with FAODs cannot
properly break down fat from either
the food they eat or from fat stored in
their bodies.

The symptoms and treatment vary


between different FAODs. They can
also vary from person to person with
the same FAOD. See the fact sheets
for each specific FAOD.
Energy from fat keeps us going

FAODs are inherited in an autosomal whenever our bodies run low of their
recessive manner and affect both main source of energy, a type of sugar

males and females. called glucose. Our bodies rely on fat


when we dont eat for a stretch of time

What causes VLCADD? like when we miss a meal or when we

VLCADD occurs when an enzyme, sleep.

called "very long chain acyl-CoA


dehydrogenase" (VLCAD) is either

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When the VLCADD enzyme is missing irritable mood


or not working, the body cannot break poor appetite
down fat for energy and must rely
Some of these other symptoms may
solely on glucose. Although glucose is
also follow:
a good source of energy, there is a
fever
limited amount available. Once the
nausea
glucose has been used up, the body
diarrhea
tries to use fat without success. This
vomiting
leads to low blood sugar, called
hypoglycemia
hypoglycemia, and to the build up of
harmful substances in the blood.
If a metabolic crisis is not treated, a
child with VLCADD can develop:
If VLCADD is not treated, what
breathing problems
problems occur?
seizures
VLCADD is variable and can cause
coma, sometimes leading to
mild effects in some people and more
death
serious health problems in others.
Symptoms may start in infancy or not
Periods of hypoglycemia can happen
until adulthood. There are three forms
with or without the other symptoms.
of VLCADD: Early, Childhood and Hypoglycemia can cause a child to feel
Adult. weak, shaky or dizzy with clammy, cold
skin. If not treated, it can lead to coma,
It is common for babies and children
and possibly death.
with the early and childhood types of
VLCADD to have episodes of illness Either hypoglycemia or a full metabolic
called metabolic crises. Some of the crisis can occur:
first symptoms of a metabolic crisis
are: after going too long without food
extreme sleepiness during illness or infection
behavior changes after heavy exercise

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Symptoms of early and childhood periods of not eating. Other effects can
VLCADD often happen after a period of include:
having nothing to eat for more than a
enlarged liver
few hours. Symptoms are also more
other liver problems
likely when a child with VLCADD gets
muscle weakness, especially
sick or has an infection.
after exercise
Early VLCADD
Heart problems are usually not seen in
About half of babies diagnosed with
childhood VLCADD.
VLCADD have the early type. They
usually start to show effects between Some children with VLCADD have
birth and 4 months. In addition to never had symptoms and are only
metabolic crises, babies can also have:
found to be affected after a brother or
sister has been diagnosed.
enlarged heart, irregular
heartbeat and other heart Adult VLCADD
problems
About one fifth of people with VLCADD
enlarged liver and other liver
have the adult type. They usually show
problems
symptoms starting in the teen years or
muscle problems in adulthood. Periods of muscle
weakness are common. Breakdown of
If not treated, babies with early
muscle fibers can occur. This usually
VLCADD usually die young.
happens during heavy exercise or after
Childhood VLCADD going without food for a long period of
About one third of people with time.
VLCADD have the childhood type. Signs of muscle breakdown are:
They usually show symptoms in late
muscle aches
infancy or early childhood. Episodes of
weakness
hypoglycemia or full metabolic crisis
cramps
happen during illness or after long

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Reddish-brown color to the your child needs to be fed. In general,


urine. it is often suggested that infants be fed
every four to six hours. Some babies
Adults with muscle symptoms who do
need to eat even more frequently than
not get treatment can develop kidney
this. It is important that infants be fed
failure.
during the night. They may need to be
woken up to eat if they do not wake up
People with the adult form of VLCADD
on their own. Your metabolic doctor
usually do not have heart problems,
and dietician will give you an
hypoglycemia or metabolic crises.
appropriate feeding plan for your
What is the treatment for VLCADD? infant. Your doctor will also give you a
Your baby's primary doctor will work sick day plan tailored to your childs
with a metabolic doctor to care for your needs for you to follow during illnesses
child. Your doctor may also suggest or other times when your child will not
that you meet with a dietician familiar eat.
with VLCADD.
Your metabolic doctor will continue to
Certain treatments may be advised for advise you on how often your child
some children but not others. When should eat as he or she gets older.
necessary, treatment is usually needed When they are well, many teens and
throughout life. The following are adults with VLCADD can go without
treatments often recommended for food for up to 12 hours without
children with VLCADD: problems. The other treatments usually
need to be continued throughout life.
1. Avoid going a long time without
food 2.Diet
Infants and young children with Sometimes a low fat, high
VLCADD need to eat frequently to carbohydrate diet is recommended.
prevent a metabolic crisis. Your food plan is recommended.
metabolic doctor will tell you how often Carbohydrates give the body may types

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of sugar that can be used as energy. In need to get a prescription from your
fact, for children needing this doctor to get MCT oil.
treatment, most food in the diet should
Some children may be helped by taking
be carbohydrates (bread, pasta, fruit,
L-carnitine. This is a safe and natural
etc.) and protein (lean meat and low-fat
substance that helps the body make
dairy foods). Any diet changes should
energy. It also helps the body get rid of
be made under the guidance of an
harmful wastes. Your doctor will
experienced dietician.
decide whether your child needs L-
People with VLCADD cannot use carnitine. Unless you are advised
certain building blocks of fat called otherwise, use only L-carnitine
long chain fatty acids. Your dietician prescribed by your doctor.
can help create a food plan low in these
Do not use any medication or
fats. Much of the rest of fat in the diet
supplement without checking with your
may be in the form of medium chain
doctor.
fatty acids.

Call your doctor at the start of any


Ask your doctor whether your child
illness
needs to have any changes in his or her
diet. Always call your health care provider
when your child has any of the
3. MCT oil and L-carnitine
following:
Medium Chain Triglyceride oil (MCT
oil) is often used as part of the food
poor appetite
plan for people with VLCADD. This low energy or excessive
special oil has medium chain fatty
sleepiness
acids that can be used in small
vomiting
amounts for energy. Your metabolic
diarrhea
doctor or dietician can guide you in an infection
how to use this supplement. You will a fever

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persistent muscle pain, If muscle symptoms happen, prompt


weakness, or reddish-brown treatment is needed to prevent kidney
color to the urine damage. Children and adults with
muscle symptoms should:
Children with VLCADD need to eat
drink fluids right away
extra starchy food and drink more
eat something starchy or sugary
fluids during any illness - even if they
get to a hospital for treatment
may not feel hungry or they could
develop hypoglycemia or a metabolic To help prevent muscle symptoms:
crisis. When they become sick, avoid prolonged or heavy
children with VLCADD often need to be exercise
treated in the hospital to prevent keep the body warm
serious health problems. eat carbohydrates before and
during periods of moderate
Ask your metabolic doctor if you
exercise
should carry a special travel letter with
medical instructions for your childs What happens when VLCADD is
care. treated?

4. Avoid prolonged exercise or With prompt and careful treatment,


exertion. people with the childhood and adult
Long periods of exercise can also forms of VLCADD can often live
trigger symptoms. Problems occurring healthy lives with typical growth and

during or after exercise can include: development. Before diagnosis through


newborn screening was available, the
muscle aches early form of VLCADD was fatal. Now,
weakness with immediate and ongoing treatment,
cramps many infants with VLCADD are
Reddish-brown color to the surviving.
urine.

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What causes the VLCAD enzyme to When both parents are carriers, there
be absent or not working correctly? is a 25% chance in each pregnancy for
Genes tell the body to make various the child to have VLCADD. There is a
enzymes. People with VLCADD have a 50% chance for the child to be a carrier,
pair of genes that do not work just like the parents. And, there is a
correctly. Because of the changes in 25% chance for the child to have two
this pair of genes, the VLCAD enzyme working genes.
either does not work properly or is not
Genetic counseling is available to
made at all.
families who have children with
How is VLCADD inherited?

VLCADD is inherited in an autosomal


recessive manner. It affects both boys
and girls equally.

Everyone has a pair of genes that make


the VLCAD enzyme. In children with
VLCADD, neither of these genes works
correctly. These children inherit one
non-working gene for the condition
from each parent.

Parents of children with VLCADD are


rarely affected with the disorder.
Instead, each parent has a single non-
working gene for VLCADD. They are
VLCADD. Genetic counselors can
called carriers. Carriers do not have
answer your questions about how
VLCADD because the other gene of
VLCADD is inherited, options during
this pair is working correctly.
future pregnancies, and how to test

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other family members. Ask your doctor Yes, it is possible to test for VLCADD
about a referral to a genetic counselor. during pregnancy. The sample needed
for this test is obtained by either CVS
Is there genetic testing available?
or amniocentesis.
Genetic testing for VLCADD can be
done on a blood sample. Genetic Parents may either choose to have
testing, also called DNA testing, looks testing during pregnancy or wait until
for changes in the pair of genes that birth to have the baby tested. A genetic
causes VLCADD. counselor can talk to you about your
choices and answer other questions
DNA testing is often used to diagnose
you may have about prenatal testing or
VLCADD in children. In addition to
testing your baby after birth.
establishing a diagnosis, DNA testing
can also tell what type of VLCADD a Can other members of the family
person has early, childhood or adult. have VLCADD or be carriers?
It can also be helpful for carrier testing
Having VLCADD
or prenatal diagnosis, discussed below.
The brothers and sisters of a baby with
Talk with your metabolic doctor or
VLCADD have a chance of being
genetic counselor about whether DNA
affected, even if they havent had
testing for VLCADD would be helpful
symptoms. Finding out whether other
to you.
children in the family have VLCADD is
What other testing is available? important because early treatment may
VLCADD can be confirmed by a special prevent serious health problems. Talk
test called a "fatty acid oxidation to your doctor or genetic counselor
probe using a skin sample. Talk to about testing your other children for
your doctor or genetic counselor if you VLCADD.
have questions about testing for
VLCADD Carriers
VLCADD.
Brothers and sisters who do not have
Can you test during pregnancy? VLCADD still have a chance to be

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carriers like their parents. Except in abnormal fat storage in the liver
special cases, carrier testing should severe bleeding
only be done in people over 18 years of
All women with a family history of
age.
VLCADD should share this information
Each of the parents brothers and with their obstetricians and other
sisters has a 50% chance to be a health care providers before and during
VLCADD carrier. It is important for any future pregnancies. Knowing about
other family members to be told that these risks allows early treatment.
they could be carriers. There is a small
Can other family members be tested?
chance they are also at risk to have
children with VLCADD. Diagnostic testing
Brothers and sisters of a child with
All states offer newborn screening for
VLCADD can have special testing to
VLCADD. However, when both parents
check for this disorder. Ask you
are carriers, newborn screening results
metabolic doctor whether your other
are not sufficient to rule out VLCADD
children should be tested for VLCADD.
in a newborn baby. In this case, special
diagnostic testing should be done in
Carrier testing
addition to newborn screening. Carrier testing may be available to
other family members. Your metabolic
During pregnancy, women carrying
doctor or genetic counselor can advise
fetuses with VLCADD may be at
you about carrier testing. .
increased risk to develop serious
medical problems. A small number of Where can Confirmatory Testing be
women are known to have developed:
done for this condition?
The confirmatory test for the diagnosis
excessive vomiting
is done by Gas Chromatography Mass
abdominal pain
Spectrometry (GC/MS) using urine
high blood pressure
sample or by Carrier gene analysis for
jaundice

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ACADVL gene extracted from either have symptoms of the condition and
patient lymphocytes (EDTA or Heparin are thought to have the childhood or
whole blood sample) or skin fibroblasts adult forms of VLCADD.
collected at 2-6 months of age.
Does VLCADD happen more
Center frequently in a certain ethnic group?
PreventiNe Lifecare Pvt. Ltd. No, VLCADD does not happen more
RPT House, Plot No. 6, Sector 24, often in any specific race, ethnic group,
Turbhe, Navi Mumbai 400705 geographical area or country.
Ph: 022-61980000/11
Does VLCADD go by any other
Academic Medical Center names?
Laboratory Genetic Metabolic VLCADD is sometimes also called:
Diseases (F0-132)
Meibergdreef 9 VLCAD deficiency

1105 AZ Amsterdam ACADVL deficiency

The Netherlands
Where can I find more information?
Ph: +31 20 5662026 / 5393
Fatty Oxidation Disorders (FOD)
E-mail: gmz_enzym@amc.nl
Family Support Group

What is the cost of the confirmatory http://www.fodsupport.org

test?
United Mitochondrial Disease

350 (+ 100 for fibroblast culturing) Foundation


http://www.umdf.org
How many people have VLCADD?
Originally thought to be rare, newborn Genetic Alliance

screening has shown that about 1 in http://www.geneticalliance.org

30,000 people have VLCADD. Some


Genetic Metabolic Dietitians
people diagnosed with VLCADD
International
through newborn screening do not
http://www.gmdi.org/index.php?option

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=com_content&view=article&id=43:vlca
d&catid=7:resourcesx

Mito Action
http://www.mitoaction.org/

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B
What is the cost of the
eta ketothiolase

confirmatory test?
deficiency How many people have BKD?
Does BKD happen more often in a
Disease name: Beta ketothiolase certain ethnic group?
deficiency Does BKD go by any other
Acronym: BKD names?
Where can I find more
What is BKD?
information?
What causes BKD?
If BKD is not treated, what This fact sheet has general information
problems occur? about BKD. Every child is different and
What is the treatment for BKD? some of these facts may not apply to
What happens when BKD is your child specifically. Certain
treated? treatments may be recommended for
What causes the MAT enzyme to some children but not others. All
be absent or not working children with BKD should be followed
correctly? by a metabolic doctor in addition to
How is BKD inherited? their primary doctor.
Is genetic testing available?
What is BKD?
What other testing is available?
BKD stands for beta ketothiolase
Can you test during pregnancy?
deficiency. It is one type of organic
Can other members of the family
acid disorder. People with BKD have
have BKD or be carriers?
problems breaking down an amino acid
Can other family members be
called isoleucine from the food they eat.
tested?
Where can Confirmatory Testing
be done for this condition?

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What causes BKD?


Organic Acid Disorders:
In order for the body to use protein
Organic acid disorders (OAs) are a from the food we eat, it is broken down
group of rare inherited conditions. into smaller parts called amino acids.
They are caused by enzymes that do Special enzymes then make changes to
not work properly. A number of the amino acids so the body can use
enzymes are needed to process them.
protein from the food we eat for use by
the body. Problems with one or more BKD occurs when an enzyme, called

of these enzymes can cause an mitochondrial acetoacetyl-CoA

organic acid disorder. thiolase (MAT), is either missing or


not working properly. This enzymes
People with organic acid disorders job is to help break down the amino
cannot break down protein properly. acid isoleucine. When a child with BKD
This causes harmful substances to eats food containing isoleucine,
build up in their blood and urine. harmful substances called organic
These substances can affect health, acids build up in the blood and cause
growth and learning. problems. Isoleucine is found in all
foods that contain protein.
The symptoms and treatment vary
between different organic acid If BKD is not treated, what problems
disorders. They can also vary from occur?
person to person with the same Each child with BKD has slightly
organic acid disorder. See the fact different effects. The first symptoms
sheets for each specific organic acid often start around age one, although
disorder. babies can show signs either earlier or
later than this. Some people with BKD
Organic acid disorders are inherited
never develop symptoms.
in an autosomal recessive manner
and affect both males and females.

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BKD can cause episodes of illness


called metabolic crises. Some of the
first symptoms of a metabolic crisis
are:

extreme sleepiness or lack of


energy
vomiting
diarrhea
fever
poor appetite
ketones in the urine (substances
created during the breakdown of
fat)

Other symptoms then follow:


increased levels of acidic
substances in the blood, called
metabolic acidosis
low blood sugar, called Other long-term effects of untreated
hypoglycemia BKD can include:
coma, sometimes leading to mental retardation
death enlarged heart with irregular
heart beat
Episodes of metabolic crisis can be
poor growth
triggered by:
abnormal muscle tone (too
going too long without food
floppy or too rigid)
illness or infection
jerky uncoordinated movements
eating too much protein
low platelets

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low level of white blood cells only L-carnitine prescribed by your


(increasing the risk of infection) doctor. Do not use any medication
without checking with your metabolic
Some people with BKD never have
doctor.
symptoms and are only found to be
affected after a brother or sister is Children with symptoms of a metabolic
diagnosed. crisis need to be treated in the hospital.
During a metabolic crisis, your child
What is the treatment for BKD?
may be given medications such as
Your babys primary doctor will work
bicarbonate by IV to help reduce the
with a metabolic doctor and a dietician
acid levels in the blood. In addition,
to care for your child.
glucose is often given by IV to prevent
the breakdown of body stores of
Prompt treatment is needed to prevent
protein. Ask your metabolic doctor if
metabolic crises and the health effects
you should carry a special travel letter
that follow. When necessary, treatment
with medical instructions for your
is usually needed throughout life.
childs care.
The following are treatments
2. Avoid going a long time without
sometimes advised for babies and
food
children with BKD:
Some infants and young children with
1. Medication BKD need to eat frequently to prevent a
Some children may be helped by taking metabolic crisis. Your metabolic doctor
L-carnitine by mouth. This is a safe will tell you how often your child needs
and natural substance that helps body to be fed. Your doctor will also give you
cells make energy. It also helps the a sick day plan, tailored to your
body get rid of harmful wastes. Your childs needs, for you to follow during
doctor will decide whether or not your illnesses or other times when your
child needs L-carnitine supplements. child will not eat.
Unless you are advised otherwise, use

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Your metabolic doctor will continue to If it is necessary for your child to eat a
advise you on how often your child low-protein diet, your dietician can
should eat as he or she gets older. help you create a food plan that meets
When they are well, many teens and your childs needs. Any diet changes
adults with BKD can go without food should be made under the guidance of
for up to 12 hours without problems. a dietician.
The other treatments usually need to
4. Tracking ketone levels
be continued throughout life.
Periodic urine tests to test the level of
3. Low-protein diet ketones may be necessary. This can be
Some children may be able to eat done at home or at the doctors office.
normal amounts of protein, but others Ketones are substances formed when
will need to be on a low-protein diet. body fat is broken down for energy.
This happens after going without food
Foods high in protein that may need to
for long periods of time, during illness,
be limited include:
or during periods of heavy exercise.
milk and dairy products
Ketones in the urine may signal the
meat and poultry
start of a metabolic crisis.
fish
eggs 5. Call your doctor at the start of any
dried beans illness
nuts and peanut butter In some children, even minor illness
can lead to a metabolic crisis. In order
Eating large amounts of these foods
to prevent problems, call your doctor
can cause protein levels to become too
right away when your child has any of
high, causing illness. However, do not
the following:
remove all protein from the diet.
Children with BKD need a certain loss of appetite
amount of protein to grow properly. vomiting
diarrhea
infection or illness

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fever Genes tell the body to make various


enzymes. People with BKD have a pair
When your child is ill, he or she needs
of genes that do not work correctly.
extra fluids and carbohydrates to
Because of the changes in this pair of
prevent a metabolic crisis. Whenever
genes, the MAT enzyme either does not
your child becomes ill, it is important to
work properly or is not made at all.
restrict protein and give him or her
extra starchy or sugary foods. How is BKD inherited?
BKD is inherited in an autosomal
What happens when BKD is treated?
recessive manner. It affects both boys
If treatment is started early and
and girls equally.
metabolic crises do not occur, your
child is likely to have normal growth Everyone has a pair of genes that make
and intelligence. Even with treatment, the MAT enzyme. In children with
some children still have repeated BKD, neither of these genes works
episodes of metabolic crises, which can correctly. These children inherit one
cause brain damage. This can result in non-working gene for the condition
learning disabilities, mental retardation from each parent.
or other problems.
Parents of children with BKD rarely
Between episodes of metabolic crisis, have the condition themselves. Instead,
people with BKD are usually healthy. each parent has a single non-working
Metabolic crises tend to happen less gene for BKD. They are called carriers.
often as a child gets older. They are Carriers do not have BKD because the
rare in children older than 10. other gene of this pair is working
correctly.
What causes the MAT enzyme to be
absent or not working correctly?

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When both parents are carriers, there pregnancies, and how to test other
is a 25% chance in each pregnancy for family members. Ask your doctor about
the child to have BKD. There is a 50% a referral to a genetic counselor.
chance for the child to be a carrier, just
Is genetic testing available?
like the parents. And, there is a 25%
Genetic testing for BKD is available.
chance for the child to have two
Genetic testing, also called DNA
testing, looks for changes in the pair of
genes that causes BKD. Talk with your
genetic counselor or metabolic doctor
if you have questions about DNA
testing.

DNA testing is not necessary to


diagnose your child. It can be helpful
for carrier testing or prenatal
diagnosis, discussed below.

What other testing is available?


Special tests on urine, blood or skin
samples can be done to help confirm
BKD. Talk to your doctor or your
genetic counselor if you have
questions about testing for BKD.

working genes.
Can you test during pregnancy?

Genetic counseling is available to If both gene changes have been found

families who have children with BKD. in your child, DNA testing can be done

Genetic counselors can answer your during future pregnancies. The sample

questions about how the condition is needed for this test is obtained by

inherited, choices during future either CVS or amniocentesis.

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If DNA testing is not possible, an like their parents. Except in special


enzyme test can be done using cells cases, carrier testing should only be
from the fetus. The sample needed for done in people over 18 years of age.
this test is obtained by either CVS or
Each of the parents brothers and
amniocentesis.
sisters has a 50% chance to be a
Parents may choose to have testing carrier. It is important for other family
during pregnancy or wait until birth to members to be told that they could be
have the baby tested. A genetic carriers. There is a small chance they
counselor can talk to you about your are also at risk to have children with
choices and answer questions about BKD.
prenatal testing or testing your baby
All states offer newborn screening for
after birth.
BKD. However, when both parents are
Can other members of the family carriers, newborn screening results are
have BKD or be carriers? not sufficient to rule out BKD in a
Having BKD newborn baby. In this case, special
Older brothers and sisters of a baby diagnostic testing should be done in
with BKD may have a small chance of addition to newborn screening.
being affected, even if they havent had
symptoms. Finding out whether other
children in the family have BKD is
Can other family members be tested?
important because early treatment may
prevent serious health problems. Talk Diagnostic testing
with your metabolic doctor or genetic Brothers and sisters can be tested
counselor about testing your other using blood, urine or skin samples.
children.
Carrier testing
BKD carriers If both gene changes have been found
Brothers and sisters who do not have in your child, other family members
BKD still have a chance to be carriers

217 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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BABYSHIELD TMS FACT SHEET

can have DNA testing to see if they are 1105 AZ Amsterdam


carriers. the Netherlands
Ph: +31 20 5662026 / 5393
If DNA testing is not possible or is not
E-mail: gmz_enzym@amc.nl
helpful, other methods of carrier testing
may be available. Your metabolic What is the cost of the confirmatory
doctor or genetic counselor can answer test?
your questions about carrier testing.
350 (+ 100 for fibroblast culturing)
Where can Confirmatory Testing be
How many people have BKD?
done for this condition?

BKD is thought to be rare. The actual


The confirmatory test for the diagnosis
incidence is unknown.
is done by Gas Chromatography Mass
Spectrometry (GC/MS) using urine Does BKD happen more frequently in
sample or confirmatory testing is done
a certain ethnic group?
by estimation of Beta- ketothiolase (2-
methyl-acetoacetyl-CoA lyase) enzyme No, BKD does not happen more often
activity in fibroblast culture from skin in any specific race, ethnic group,
biopsy specimen from patient. geographical area or country.

Center Does BKD go by any other names?


PreventiNe Lifecare Pvt. Ltd.
BKD is also sometimes called:
RPT House, Plot No. 6, Sector 24,
Turbhe, Navi Mumbai 400705 Ketone utilization disorder
Ph: 022-61980000/11 Alpha-methylacetoacetic

Academic Medical Center aciduria

Laboratory Genetic Metabolic Diseases 2-methyl-3-hydroxybutyric

(F0-132) acidemia

Meibergdreef 9 Mitochondrial acetoacetyl-CoA


thiolase deficiency

218 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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MAT deficiency
T2 deficiency
3-oxothiolase deficiency
3-ketothiolase deficiency
3-KTD deficiency

Where can I find more information?

Organic Acidemia Association


http://www.oaanews.org

CLIMB (Children Living with Inherited


Metabolic Diseases)
http://www.climb.org.uk

Save Babies through Screening


Foundation
http://www.savebabies.org

Genetic Alliance
http://www.geneticalliance.org/

Ketone Utilization Disorder: A Guide


for Parents (PacNoRGG publication)
http://www.westernstatesgenetics.org/
pacnorgg/PDFs_all-
081409/ketone_util_eng.pdf

219 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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G
How many people have GA-1?
lutaric acidemia,

Does GA-1 happen more often in a


type 1 certain ethnic group?
Does GA-1 go by any other
Disease name: Glutaric acidemia, names?
type 1 Where can I find more
Acronym: GA-1 information?

What is GA-1? This fact sheet contains general


What causes GA-1? information about GA-1. Every child is
If GA-1 is not treated, what different and some of these facts may
problems occur? not apply to your child specifically.
What is the treatment for GA-1? Certain treatments may be
What happens when GA-1 is recommended for some children but
treated? not others. All children with GA-1
How is GA-1 inherited? should be followed by a metabolic
Is genetic testing available? doctor in addition to their primary
What other testing is available? doctor.
Can you test during pregnancy?
What is GA-1?
Can other members of the family
GA-1 stands for glutaric acidemia,
have GA-1 or be carriers?
type 1. It is one type of organic acid
Can other family members be
disorder. People with GA-1 have
tested?
problems breaking down the amino
Where can Confirmatory Testing
acids lysine, and tryptophan from the
be done for this condition?
food they eat.
What is the cost of the
confirmatory test?

220 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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What causes GA-1? into smaller parts called amino acids.


Special enzymes then make changes to
In order for the body to use protein
the amino acids so the body can use
from the food we eat, it is broken down
them.

Organic Acid Disorders:


GA-1 occurs when an enzyme called

Organic acid disorders (OAs) are a "glutaryl-CoA dehydrogenase" is either

group of rare inherited conditions. missing or not working properly. This

They are caused by enzymes that do enzyme's job is to break down a

not work properly. A number of substance called glutaryl-CoA.

enzymes are needed to process Glutaryl-CoA is made when the amino

protein from the food we eat for use by acids lysine, hydroxylysine and

the body. Problems with one or more tryptophan are processed. It cannot be

of these enzymes can cause an removed and it causes glutaric acid

organic acid disorder. and other harmful substances build up


in the blood and cause problems.
People with organic acid disorders Lysine and tryptophan are found in all
cannot break down protein properly. foods that contain protein.
This causes harmful substances to
build up in their blood and urine. If GA-1 is not treated, what problems

These substances can affect health, occur?

growth and learning. Babies with GA-1 are usually healthy at


birth, although many are born with a
The symptoms and treatment vary larger than average head size. Other
between different organic acid symptoms usually start between two
disorders. They can also vary from months and four years of age.
person to person with the same
organic acid disorder. See the fact GA-1 causes episodes of severe illness

sheets for each specific organic acid called metabolic crises. Some of the

disorder. first symptoms of a metabolic crisis


are:
Organic acid disorders are inherited
221 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY
in an autosomal recessive manner
Unauthorised reproduction of this article is prohibited
and affect both males and females.
BABYSHIELD TMS FACT SHEET

poor appetite
extreme sleepiness or lack of
energy
irritability
jitteriness
nausea
vomiting
low muscle tone (floppy muscles
and joints)
muscle weakness

If untreated, other symptoms then


follow:
tics or spasms of the muscles
rigid muscle contractions called
spasticity
involuntary jerking movements
of the arms and legs, called Episodes of metabolic crisis are often
dystonia triggered by:

poor coordination and balance illness or infection

problems fever

increased levels of acidic going without food for long

substances in the blood, called periods of time

metabolic acidosis
Other effects of GA-1 that can happen
seizures
even without a metabolic crisis are:
swelling of the brain or blood in
poor growth
the brain
enlarged liver
coma, sometimes leading to
low muscle tone
death
progressive spasticity

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dystonia, an involuntary The following are treatments often


movement disorder recommended for babies and children
repeated episodes of fever with GA-1:
excessive sweating
1.Medication
delays in walking and other
Riboflavin is a vitamin that helps the
motor skills
body process protein. It may also help
learning delays and mental
lessen the amount of glutaric acid
retardation
made by the body. Your doctor may
speech problems
recommend that your child take
brain damage
riboflavin supplements by mouth.
Some people have very mild or no
Some children may be helped by L-
symptoms and are only found to be
carnitine. This is a safe and natural
affected after a brother or sister is
substance that helps body cells make
diagnosed.
energy. It also helps the body get rid of
What is the treatment for GA-1? harmful wastes. Your doctor will
decide whether or not your child needs
Your babys primary doctor will work
L-carnitine supplements. Unless you
with a metabolic doctor and a dietician
are advised otherwise, use only L-
to care for your child.
carnitine prescribed by your doctor.

Prompt treatment is needed to prevent


Do not use any medication without
episodes of metabolic crisis. You need
checking with your metabolic doctor.
to start treatment as soon as you know
your child has GA-1. Certain Children with symptoms of a metabolic
treatments may be advised for some crisis need medical treatment right
children but not others. Treatment is away. They often need to be treated in
usually needed throughout life. the hospital. During a metabolic crisis,
children may be given fluids, glucose,
insulin, carnitine and other

223 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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medications by IV to help get rid of should eat as he or she gets older.


harmful substances in the blood. Ask When they are well, many older
your metabolic doctor if you should children and adults with GA-1 can go
carry a special travel letter with without food for up to 12 hours without
medical instructions for your childs problems. They may need to continue
care. the other treatments throughout life.

2. Avoid going a long time without 3. Food plan, including medical


food foods and formula
Infants and young children with GA-1
Most children need to eat a diet made
need to eat frequently to prevent a
up of foods low in lysine and
metabolic crisis. Your metabolic doctor
tryptophan. Special medical foods and
will tell you how often your child needs
a special formula are usually part of the
to be fed. In general, it is often
diet. Your dietician will create a food
suggested that infants be fed every four
plan that has the right amount of
to six hours. Some babies need to eat
protein, nutrients, and energy for your
even more frequently than this. It is
child.
important that infants be fed during the
night. They may need to be woken up
Low-protein (lysine and tryptophan)
to eat if they do not wake up on their diet
own. Your metabolic doctor and Foods that will need to be avoided or
dietician will give you an appropriate strictly limited include:
feeding plan for your infant. Your
milk, cheese, and other dairy
doctor will also give you a sick day
products
plan, tailored to your childs needs, for
meat and poultry
you to follow during illnesses or other
fish
times when your child will not eat. eggs
dried beans and legumes
Your metabolic doctor will continue to
nuts and peanut butter
advise you on how often your child

224 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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Many vegetables and fruits have only her age, weight, general health, and
small amounts of lysine and tryptophan blood test results. Your dietician will
and can be eaten in carefully measured fine-tune your childs diet over time.
amounts.
The long-term benefits of the special
Do not remove all protein from the diet. diet and medical foods are not yet
Your child still needs a certain amount known. However, it is important to
of protein for normal growth and follow the food plan as long as your
development. Any changes in the diet doctor advises.
should be made under the guidance of
4. Regular blood tests
a dietician familiar with GA-1.
Your child will have regular blood tests
Medical foods and formula to measure his or her amino acid levels.
There are medical foods such as Urine tests may also be done. Your
special low-protein flours, pastas, and childs diet and medication may need to
rice that are made especially for people be adjusted based on blood and urine
with organic acid disorders. test results.

A special medical formula that contains 5. Call your doctor at the start of any
the right level of amino acids and illness
nutrients for your child may be For some babies and children, even
recommended. Your metabolic doctor minor illness can lead to a metabolic
and dietician will tell you whether your crisis. In order to prevent problems,
child should be on this formula and call your doctor right away when your
how much to use. Some states offer child has any of the following:
help with payment, or require private
loss of appetite
insurance to pay for the formula and
low energy or extreme
other special medical foods.
sleepiness
Your childs exact food plan will vomiting
depend on many things such as his or fever

225 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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infection or illness After age six, metabolic crises are less


behavior or personality changes common.

Children with GA-1 need to eat more What causes the glutaryl-CoA
carbohydrates and drink more fluids dehydrogenase enzyme to be absent
when they are ill even if theyre not or not working correctly?
hungry or they could have a
Genes tell the body to make various
metabolic crisis.
enzymes. People with GA-1 have a pair

Children who are sick often dont want of genes that do not work correctly.

to eat. If they cant eat, or if they show Because of the changes in this pair of
signs of a metabolic crisis, they may genes, the glutaryl-CoA dehydrogenase
need to be treated in the hospital. Ask enzyme either does not work properly
your metabolic doctor if you should or is not made at all.

carry a special travel letter with


How is GA-1 inherited?
medical instructions for your childs
care. GA-1 is inherited in an autosomal
recessive manner. It affects both boys
What happens when GA-1 is treated?
and girls equally.
With prompt and lifelong treatment,
children with GA-1 can often live Everyone has a pair of genes that make
healthy lives with typical growth and the glutaryl-CoA dehydrogenase
learning. Early treatment can help enzyme. In children with GA-1, neither
prevent episodes of metabolic crisis of these genes works correctly. These
and the resulting health effects. children inherit one non-working gene
for the condition from each parent.
Even with treatment, some children
continue to have episodes of metabolic Parents of children with GA-1 rarely
crisis. This can lead to brain damage have the condition themselves. Instead,
and long-term problems with each parent has a single non-working
involuntary movements and spasticity. gene for GA-1. They are called carriers.

226 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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Carriers do not have GA-1 because the questions about how the condition is
other gene of this pair is working inherited, choices during future
correctly. pregnancies, and how to test other
family members. Ask your doctor about
When both parents are carriers, there
a referral to a genetic counselor.
is a 25% chance in each pregnancy for
the child to have GA-1. There is a 50% Is genetic testing available?
chance for the child to be a carrier, just Genetic testing for GA-1 can be done
like the parents. And, there is a 25% on a blood sample. Genetic testing,
chance for the child to have two also called DNA testing, looks for
working genes. changes in the pair of genes that cause
GA-1.

DNA testing is not necessary to


diagnose your child. It can be helpful
for carrier or prenatal testing,
discussed below.

What other testing is available?


Special tests on blood, urine, or skin
samples can be done to confirm GA-1.
Talk to your metabolic doctor or
genetic counselor if you have questions
about testing for GA-1.

Can you test during pregnancy?


If both gene changes have been found
in your child, DNA testing can be done
during future pregnancies. The sample
Genetic counseling is available to
families who have children with GA-1. needed for this test is obtained by
either CVS or amniocentesis.
Genetic counselors can answer your

227 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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BABYSHIELD TMS FACT SHEET

If DNA testing would not be helpful, an cases, carrier testing should only be
enzyme test can be done on cells from done in people over 18 years of age.
the fetus. The sample needed for this
Each of the parents brothers and
test is obtained by either CVS or
sisters has a 50% chance to be a
amniocentesis.
carrier. It is important for other family
Parents may choose to have testing members to be told that they could be
during pregnancy or wait until birth to carriers. There is a small chance they
have the baby tested. A genetic are also at risk to have children with
counselor can talk to you about your GA-1.
choices and answer questions about
All states offer newborn screening for
prenatal testing or testing your baby
BKD. However, when both parents are
after birth.
carriers, newborn screening results are
Can other members of the family not sufficient to rule out BKD in a
have GA-1 or be carriers? newborn baby. In this case, special
Having GA-1 diagnostic testing should be done in
The brothers and sisters of a baby with addition to newborn screening.
GA-1 have a chance of being affected,
Can other family members be tested?
even if they havent had symptoms.
Finding out whether other children in Diagnostic testing
the family have GA-1 is important
Brothers and sisters of a child with GA-
because early treatment may prevent
1 can be tested using blood, urine or
serious health problems. Talk to your
skin samples.
metabolic doctor or genetic counselor
about testing your other children. Carrier testing
If both gene changes have been found
GA-1 carrier
in your child, other family members
Brothers and sisters who do not have can have DNA testing to see if they are
GA-1 still have a chance to be carriers carriers.
like their parents. Except in special

228 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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If DNA testing would not be helpful, E-mail: gmz_enzym@amc.nl


other methods of carrier testing may be
What is the cost of the confirmatory
available. Your metabolic doctor or
test?
genetic counselor can answer your
questions about carrier testing.
350 (+ 100 for fibroblast culturing)

Where can Confirmatory Testing be How many people have GA-1?


done for this condition?
About one in every 40,000 white babies
in the United States is born with GA-1.
The confirmatory test for the
diagnosis is done by Gas Does GA-1 happen more frequently in
Chromatography Mass Spectrometry
a certain ethnic group?
(GC/MS) using urine sample.
GA-1 occurs in people from all parts of
Or by estimation of Glutaryl-CoA
the world. It is more common in people
dehydrogenase activity in the cultured of Amish background in the United
skin fibroblasts or peripheral blood States, the Ojibway Indian population
mononuclear lymphocytes.
in Canada, and people of Swedish

Center ancestry.

PreventiNe Lifecare Pvt. Ltd.


RPT House, Plot No. 6, Sector 24,
Turbhe, Navi Mumbai 400705
Ph: 022-61980000/11
Does GA-1 go by any other names?
Academic Medical Center GA-1 is sometimes also called:
Laboratory Genetic Metabolic Diseases
(F0-132) Glutaric aciduria type 1

Meibergdreef 9 Glutaryl-CoA dehydrogenase

1105 AZ Amsterdam deficiency

The Netherlands Dicarboxylic aminoaciduria

Ph: +31 20 5662026 / 5393

229 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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Glutarate-aspartate transport
defect

Where can I find more information?

Organic Acidemia Association


http://www.oaanews.org

CLIMB (Children Living with Inherited


Metabolic Disorders)
http://www.climb.org.uk

Save Babies through Screening


Foundation
http://www.savebabies.org/

Genetic Alliance
http://www.geneticalliance.org/

International Organization of Glutaric


Acidemia
http://helpioga.org/

230 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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H
Where can Confirmatory Testing
olocarboxylase

be done for this condition?


synthetase What is the cost of the
confirmatory test?
deficiency How many people have HCSD?
Does HCSD happen more often in
Disorder name: Holocarboxylase
a certain ethnic group?
synthetase deficiency
Does HCSD go by any other
Also known as: Multiple carboxylase
names?
deficiency - neonatal form (MCD)
Where can I find more
Acronym: HCSD
information?

What is HCSD?
This fact sheet contains general
What causes HCSD?
information about HCSD. Every child is
If HCSD is not treated, what
different and some of these facts may
problems occur?
not apply to your child specifically.
What is the treatment for HCSD?
Certain treatments may be
What happens when HCSD is
recommended for some children but
treated?
not others. All children with HCSD
What causes the HCS enzyme to
should be followed by a metabolic
be absent or not working
doctor in addition to their primary
correctly?
doctor.
How is HCSD inherited?
Is genetic testing available? What is HCSD?
What other testing is available? HCSD stands for holocarboxylase
Can you test during pregnancy? synthetase deficiency. It is one type of
Can other members of the family organic acid disorder. People with
have HCSD or be carriers? HCSD have problems changing protein
Can other family members be and carbohydrates from food into
tested? energy for the body.

231 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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What causes HCSD? This enzymes job is to add a vitamin


called biotin to other enzymes called
HCSD occurs when an enzyme called
carboxylases so that they can change
holocarboxylase synthetase (HCS), is
the food we eat into energy for the
either missing or not working properly.
body. When the HCS enzyme is not
working, certain harmful substances
Organic Acid Disorders: build up in the blood and urine. This
Organic acid disorders (OAs) are a can cause serious health problems.
group of rare inherited conditions. They
are caused by enzymes that do not work
properly. A number of enzymes are
needed to process protein from the food
we eat for use by the body. Problems
with one or more of these enzymes can
cause an organic acid disorder.

People with organic acid disorders


cannot break down protein properly.
This causes harmful substances to
build up in their blood and urine. These
substances can affect health, growth
and learning.

The symptoms and treatment vary


between different organic acid
disorders. They can also vary from
person to person with the same organic
acid disorder. See the fact sheets for If HCSD is not treated, what
each specific organic acid disorder. problems occur?

Organic acid disorders are inherited in


an autosomal recessive manner and
232 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY
affect both males and females.
Unauthorised reproduction of this article is prohibited
BABYSHIELD TMS FACT SHEET

Each child with HCSD is likely to high levels of acidic substances


experience slightly different effects. in the blood, called metabolic
Many babies with this condition start acidosis
to have symptoms within hours of birth slightly high levels of ammonia
or during the first few days or weeks of in the blood
life. Other babies have their first low platelets
symptoms sometime in infancy, usually ketones in the urine
before two years of age. high levels of substances called
organic acids in the urine
A small number of people with HCSD
never show symptoms and are only If a metabolic crisis is not treated, a
found to be affected after a brother or child with HCSD can develop:
sister is diagnosed. breathing problems
seizures
HCSD causes episodes of illness called
swelling of the brain
metabolic crises. Some of the first
coma, sometimes leading to
symptoms of a metabolic crisis are:
death
poor appetite
vomiting Untreated children with HCSD often
extreme sleepiness or lack of have other symptoms, whether or not
energy they have metabolic crises. These can
irritability include:
low muscle tone (floppy muscles skin rashes or skin infections
and joints) hair loss
severe peeling skin rash learning disabilities or mental
retardation
Common lab findings are:
delays in walking and motor
low blood sugar, called
skills
hypoglycemia
problems coordinating
movements, called ataxia

233 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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rigid muscle tone, called know your child has HCSD. Your child
spasticity will need to take biotin by mouth on a
poor growth daily basis throughout life.
seizures
Biotin is usually the only medication
hearing loss
needed to treat HCSD. Your child will
vision loss
not need to restrict any activities or
Without treatment, most babies with change his or her diet.
HCSD will die.
What happens when HCSD is
What is the treatment for HCSD? treated?
Your babys primary doctor will work Babies who receive prompt and
with a metabolic doctor to provide care ongoing treatment with biotin before
for your child. they have a metabolic crisis are
expected to have normal growth and
The main treatment for HCSD is a type
development.
of B vitamin called biotin. In babies
found to have HCSD through newborn Even with treatment, a few children
screening, biotin treatment can prevent have developed life-long learning
symptoms from occurring. It can also problems or mental retardation. In
reverse some of the health problems in children who have already shown
children who have already shown delays in learning, or loss of hearing or
symptoms. You will need a prescription eyesight, treatment can prevent
from your doctor in order to purchase additional effects. But, it may not be
the amount of biotin your child will able to correct the effects that are
need. already present.

Prompt treatment with biotin is needed What causes the HCS enzyme to be
to prevent mental retardation and absent or not working correctly?
serious medical problems. You should Genes tell the body to make various
start the treatment as soon as you enzymes. People with HCSD have a

234 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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pair of genes that do not work chance for the child to have two
correctly. Because of these gene working genes.
changes, the HCS enzyme does not
work properly or is not made at all.

How is HCSD inherited?


HCSD is inherited in an autosomal
recessive manner. It affects both boys
and girls equally.

Everyone has a pair of genes that make


the HCS enzyme. In children with
HCSD, neither of these genes works
correctly. These children inherit one
non-working gene for the condition
from each parent.

Parents of children with HCSD rarely


have the disorder. Instead, each parent
has a single non-working gene for
HCSD. They are called carriers. Genetic counseling is available to
Carriers do not have HCSD because families who have children with HCSD.

the other gene of this pair is working Genetic counselors can answer your

correctly. questions about how HCSD is


inherited, choices during future
When both parents are carriers, there pregnancies, and how to test other
is a 25% chance in each pregnancy for family members. Ask your doctor about
the child to have HCSD. There is a 50% a referral to a genetic counselor.
chance for the child to be a carrier, just
like the parents. And, there is a 25% Is genetic testing available?

235 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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BABYSHIELD TMS FACT SHEET

Genetic testing for HCSD is available. for this test is obtained by


Genetic testing, also called DNA amniocentesis.
testing, looks for changes in the pair of
Parents may either choose to have
genes that causes HCSD. Talk with
testing during pregnancy or wait until
your genetic counselor or metabolic
birth to have the baby tested. A genetic
doctor if you have questions about
counselor can talk to you about your
DNA testing.
choices and answer questions about
DNA testing is not necessary to prenatal testing or testing your baby
diagnose your child. If available, it can after birth.
be helpful for carrier testing or prenatal
Can other members of the family
diagnosis, discussed below.
have HCSD or be carriers?
What other testing is available?
Having HCSD
Special tests on blood or skin samples
Older brothers and sisters of a baby
can be done to confirm HCSD. Talk to
with HCSD have a small chance of
your metabolic doctor or genetic
being affected, even if they havent had
counselor if you have questions about
symptoms. Finding out whether other
testing for HCSD.
children in the family have this
Can you test during pregnancy? condition is important because early
If both gene changes have been found treatment may prevent serious health
in your child with HCSD, DNA testing problems. Talk to your metabolic
can be done during future pregnancies. doctor or genetic counselor about
The sample needed for this test is testing your other children.
obtained by either CVS or
HCSD carriers
amniocentesis.
Brothers and sister who do not have
An enzyme test can also be done using HCSD still have a chance to be carriers
cells from the fetus. The sample needed like their parents. Except in special

236 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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cases, carrier testing should only be Carrier testing for HCSD may be
done on people over 18 years of age. available. If you have questions about
carrier testing, ask your genetic
Each of the parents brothers and
counselor or metabolic doctor.
sisters has a 50% chance to be an
HCSD carrier. It is important for other Where can Confirmatory Testing be
family members to be told that they done for this condition?
could be carriers. There is a small
The confirmatory test for the
chance they are also at risk to have
diagnosis is done by Gas
children with HCSD.
Chromatography Mass Spectrometry
All states offer newborn screening for (GC/MS) using urine sample.
HCSD. However, when both parents
Center
are HCSD carriers, newborn screening
PreventiNe Lifecare Pvt. Ltd.
results are not sufficient to rule out the
RPT House, Plot No. 6, Sector 24,
condition in a newborn baby. In this
Turbhe, Navi Mumbai 400705
case, special diagnostic testing should
Ph: 022-61980000/11
be done in addition to newborn
screening. How many people have HCSD?
Less than one in 100,000 babies in the
Can other family members be tested?
United States is born with HCSD.

Diagnostic testing
Does HCSD happen more frequently
Diagnostic testing on blood or skin
in a certain ethnic group?
samples can be done for brothers or
No, HCSD does not happen more often
sisters of a child with HCSD. Talk to
in any specific race, ethnic group,
your doctor or genetic counselor if you
geographical area, or country.
have questions about testing for HCSD.

Does HCSD go by any other names?


Carrier testing
HCSD is sometimes also called:

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Holocarboxylase deficiency
HLCS deficiency
Multiple carboxylase deficiency,
early-onset
Infant multiple carboxylase
deficiency
MCD, neonatal form

Where can I find more information?


Organic Acidemia Association
http://www.oaanews.org

CLIMB (Children Living with Inherited


Metabolic Disorders)
http://www.climb.org.uk

Save Babies Through Screening


Foundation
http://www.savebabies.org/

Genetic Alliance
http://www.geneticalliance.org/

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3 -Hydroxy-3-
Methylglutaryl-
Can other members of the family
have HMG lyase deficiency or be
carriers?
Can other family members be
CoA Lyase tested?
Where can Confirmatory Testing
Deficiency

be done for this condition?


What is the cost of the
Disorder name: 3-hydroxy-3-
confirmatory test?
methylglutaryl-CoA lyase deficiency
How many people have HMG
Acronym: HMG lyase deficiency
lyase deficiency?
What is HMG lyase deficiency? Does HMG lyase deficiency
What causes HMG lyase happen more often in a certain
deficiency? ethnic group?
If HMG lyase deficiency is not Does HMG lyase deficiency go by
treated, what problems occur? any other names?
What is the treatment for HMG Where can I find more
lyase deficiency? information?
What happens when HMG lyase
This fact sheet contains general
deficiency is treated?
information about HMG lyase
What causes the HMG CoA lyase
deficiency. Every child is different and
enzyme to be absent or not
some of these facts may not apply to
working correctly?
your child specifically. Certain
How is HMG lyase deficiency
treatments may be recommended for
inherited?
some children but not others. All
Is genetic testing available?
children with this condition should be
What other testing is available?
followed by a metabolic doctor in
Can you test during pregnancy?
addition to their primary doctor.

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What is HMG lyase deficiency?


between different organic acid
HMG lyase deficiency is one type of
disorders. They can also vary from
organic acid disorder. People with this
person to person with the same
condition have problems breaking
organic acid disorder. See the fact
down an amino acid called leucine
sheets for each specific organic acid
from the food they eat.
disorder.

Organic acid disorders are inherited


in an autosomal recessive manner
and affect both males and females.

Organic Acid Disorders:


Organic acid disorders (OAs) are a What causes HMG lyase deficiency?

group of rare inherited conditions. In order for the body to use protein

They are caused by enzymes that do from the food we eat, it is broken down

not work properly. A number of into smaller parts called amino acids.

enzymes are needed to process Special enzymes then make changes to

protein from the food we eat for use by the amino acids so the body can use

the body. Problems with one or more them.

of these enzymes can cause an


In order for the body to use fat for
organic acid disorder.
energy, enzymes break down fatty

People with organic acid disorders acids into ketone bodies. Normally,

cannot break down protein properly. during long periods without eating,

This causes harmful substances to ketones are made by the body and used

build up in their blood and urine. for fuel.

These substances can affect health,


HMG lyase deficiency occurs when an
growth and learning.
enzyme, called HMG CoA lyase, is

The symptoms and treatment vary either missing or not working properly.
This enzyme has two jobs. The first is

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(hypoglycemia) and serious health


problems.

If HMG lyase deficiency is not


treated, what problems occur?

Each child with HMG lyase deficiency


will have somewhat different effects.
Babies with this condition are usually
healthy at birth. Most babies start to
have symptoms between 3 months and
two years of age. A few babies, though,
have had their first symptoms just a
few days after birth.

HMG lyase deficiency causes episodes


of illness called metabolic crises. Some
to help break down leucine. Leucine is of the first symptoms of a metabolic
found in all foods that contain protein. crisis are:
The second job is to help the body
poor appetite
make ketone bodies from stored fat. extreme sleepiness or lack of
energy
When children with this condition eat
behavior changes
food containing leucine, harmful
irritable mood
substances build up in the blood. In
muscle weakness
addition, children with HMG lyase
deficiency cant make ketone bodies Some or all of these symptoms may
from stored fat like most people. So, also occur:
when they dont eat for a long period of fever
time, they can develop low blood sugar nausea
diarrhea

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vomiting When a child is ill or goes without food


hypoglycemia for too long, the body breaks down its
increased levels of acidic own protein and fat to use for energy.
substances in the blood, called In people with HMG lyase deficiency,
metabolic acidosis this can trigger a metabolic crisis, as
high levels of ammonia in the described above.
blood
Between episodes of metabolic crisis,
enlarged liver
children with this condition are usually
If a metabolic crisis is not treated, a healthy.
child with HMG can develop:
Long-term effects can happen in some
breathing problems
children. These may include:
seizures
enlarged heart
coma, sometimes leading to
inflammation of the pancreas,
death
called pancreatitis
If not treated, many babies with HMG hearing loss
lyase deficiency die during their first vision loss
metabolic crisis. In surviving babies, learning disabilities or mental
repeated episodes of metabolic crisis retardation
can cause brain damage. This can
Some people with HMG lyase
result in life-long learning problems or
deficiency never have symptoms and
mental retardation.
are only found to be affected after a
Episodes of metabolic crisis can be brother or sister is diagnosed. A few
triggered by: individuals have been diagnosed after
developing heart conditions in their
illness or infection
teens and early twenties.
going without food for long
periods of time What is the treatment for HMG lyase
eating large amounts of protein deficiency?

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Your babys primary doctor will work and dietician will give you an
with a metabolic doctor and a dietician appropriate feeding plan for your
to care for your child. infant. Your doctor will also give you a
sick day plan, tailored to your childs
Prompt treatment is needed to prevent
needs, for you to follow during
metabolic crises and the health effects
illnesses or other times when your
that follow. You need to start treatment
child will not eat.
as soon as you know your child has
HMG lyase deficiency. Certain Your metabolic doctor will continue to
treatments may be advised for some advise you on how often your child
children but not others. Treatment is should eat as he or she gets older.
usually needed throughout life.
2. Low-leucine diet, including
The following are treatments often medical foods and formula
recommended for babies and children A food plan low in leucine with limited
with this condition: amounts of fat and protein is often
recommended. Most food in the diet
1. Avoid going a long time without
will be carbohydrates (bread, cereal,
food
pasta, fruit, vegetables, etc.).
Infants and young children with HMG
Carbohydrates give the body many
lyase deficiency need to eat frequently
types of sugar that can be used as
to prevent a metabolic crisis. Your
energy. Eating a diet high in
metabolic doctor will tell you how often
carbohydrates and low in protein and
your child needs to be fed. In general,
fat can help prevent low blood sugar
it is often suggested that infants be fed
and metabolic crises.
every four to six hours. Some babies
need to eat even more frequently than Foods high in protein and fat that your
this. It is important that infants be fed child may need to avoid or limit:
during the night. They may need to be milk and dairy products
woken up to eat if they do not wake up meat and poultry
on their own. Your metabolic doctor fish

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eggs metabolic doctor and dietician will


dried beans and legumes decide whether your child needs this
nuts and peanut butter formula. Some states offer help with
butter, margarine, oil, lard, and payment, or require private insurance
foods made with these fats to pay for the formula and other special
medical foods.
Many vegetables and fruits have only
small amounts of protein and fat and 3. Medications
can be eaten in carefully measured Some children may benefit by taking L-
amounts. Do not remove all protein and carnitine. This is a safe and natural
fat from the diet. Your child needs a substance that helps body cells make
certain amount of each to grow energy. It also helps the body get rid of
properly. harmful wastes. Your doctor will
decide whether or not your child needs
Your dietician will create a food plan
L-carnitine. Unless you are advised
that contains the right amount of
otherwise, use only L-carnitine
protein, fat, nutrients, and energy to
prescribed by your doctor. Do not use
keep your child healthy. Your child
any medication without checking with
may need to be on a special food plan
your doctor.
throughout life.
Children with symptoms of a metabolic
Medical foods and formula crisis need medical treatment right
There are medical foods such as away. They often need to be treated in
special low-protein flours, pastas, and the hospital. During a metabolic crisis,
rice that are made especially for people children may be given glucose,
with organic acid disorders. Your bicarbonate, and other medications by
dietician will tell you how to use these IV to treat hypoglycemia and other
foods as part of your childs diet. symptoms of a metabolic crisis. Ask
your metabolic doctor if you should
Some children are also given a special
carry a special travel letter with
leucine-free medical formula. Your

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medical instructions for your childs What happens when HMG lyase
care. deficiency is treated?
With prompt and careful treatment,
4. Call your doctor at the start of any
children with HMG lyase deficiency
illness
have a good chance to live healthy lives
In some children, even minor illnesses
with typical growth and development.
such as a cold or the flu can lead to a
metabolic crisis. In order to prevent Even with treatment, some children
problems, call your doctor right away still have repeated bouts of
when your child has any of the hypoglycemia or metabolic crises. This
following: can cause brain damage and may lead
loss of appetite to life-long learning problems or mental
vomiting retardation.
diarrhea
What causes the HMG CoA lyase
infection or illness
enzyme to be absent or not working
fever
correctly?
Children with HMG lyase deficiency Genes tell the body to make various
need to eat more carbohydrates and enzymes. People with HMG lyase
drink more fluids when they are ill deficiency have a pair of genes that do
even if theyre not hungry or they not work correctly. Because of the
could have a metabolic crisis. Also, changes in this pair of genes, the HMG
they need to avoid eating protein and CoA lyase enzyme either does not work
fat during any illness. properly or is not made at all.

Children who are ill often dont want to How is HMG lyase deficiency
eat. If they cant eat, or if they show inherited?
signs of a metabolic crisis, they may HMG lyase deficiency is inherited in an
need to be treated in the hospital. autosomal recessive manner. It affects
both boys and girls equally.

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Everyone has a pair of genes that make


the HMG CoA lyase enzyme. In
children with HMG lyase deficiency,
neither of these genes works correctly.
These children inherit one non-working
gene for the condition from each
parent.

Parents of children with HMG lyase


deficiency rarely have the disorder.
Instead, each parent has a single non-
working gene for HMG lyase
deficiency. They are called carriers.
Carriers do not have the condition
because the other gene of this pair is
working correctly.
Genetic counseling is available to
When both parents are carriers, there
families who have children with HMG
is a 25% chance in each pregnancy for
lyase deficiency. Genetic counselors
the child to have HMG lyase deficiency.
can answer your questions about how
There is a 50% chance for the child to
the condition is inherited, choices
be a carrier, just like the parents. And,
during future pregnancies, and how to
there is a 25% chance for the child to
test other family members. Ask your
have two working genes.
doctor about a referral to a genetic
counselor.

Is genetic testing available?


Genetic testing for this condition is
available. Genetic testing, also called
DNA testing, looks for changes in the

246 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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pair of genes that causes HMG lyase Testing has also been done in late
deficiency. Talk with your genetic pregnancy (after 23 weeks) using a
counselor or metabolic doctor if you urine sample from the mother.
have questions about DNA testing.
Parents may either choose to have
DNA testing is not necessary to testing during pregnancy or wait until
diagnose your child. If available, it can birth to have the baby tested. A genetic
be helpful for carrier testing or prenatal counselor can talk to you about your
diagnosis, discussed below. choices and answer questions about
prenatal testing or testing your baby
What other testing is available?
after birth.
Special tests on blood, urine, or skin
samples can be done to help confirm Can other members of the family
HMG lyase deficiency. Talk to your have HMG lyase deficiency or be
metabolic doctor or genetic counselor if carriers?
you have questions about testing for
Having HMG lyase deficiency
this condition.
The brothers and sisters of a baby with
Can you test during pregnancy? HMG lyase deficiency have a chance of
If both gene changes have been found being affected, even if they havent had
in your child, DNA testing can be done symptoms. Finding out whether other
during future pregnancies. The sample children in the family have the
needed for this test is obtained by condition is important because early
either CVS or amniocentesis. treatment may prevent serious health
problems. Talk to your metabolic
It may also be possible to do an
doctor or genetic counselor about
enzyme test using cells from the fetus.
testing your other children.
The sample needed for this test is
obtained by either CVS or
HMG lyase deficiency carriers
amniocentesis.
Brothers and sisters who do not have
HMG lyase deficiency still have a

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chance to be carriers like their parents. If both gene changes have been found
Except in special cases, carrier testing in the child with HMG lyase deficiency,
should only be done in people over 18 other family members can have DNA
years of age. testing to see if they are carriers.

Each of the parents brothers and If DNA testing is not possible or is not
sisters has a 50% chance to be a helpful, other methods of carrier testing
carrier. It is important for other family may be available. Your metabolic
members to be told that they could be doctor or genetic counselor can answer
carriers. There is a small chance they your questions about carrier testing.
are also at risk to have children with
Where can Confirmatory Testing be
HMG lyase deficiency.
done for this condition?
All states offer newborn screening for The confirmatory test for the
HMG lyase deficiency. However, when diagnosis is done by Gas
both parents are carriers for HMG lyase Chromatography Mass Spectrometry
deficiency, newborn screening results (GC/MS) using urine sample
are not sufficient to rule out the Or by estimation of 3-Hydroxy-3-
condition in a newborn baby. In this methylglutaryl-CoA lyase activity in
case, special diagnostic testing should the cultured skin fibroblasts or
be done in addition to newborn peripheral blood mononuclear
screening. lymphocytes.

Can other family members be tested? Center


PreventiNe Lifecare Pvt. Ltd.
Diagnostic testing RPT House, Plot No. 6, Sector 24,
Brothers and sisters of a child with Turbhe, Navi Mumbai 400705
HMG lyase deficiency can be tested Ph: 022-61980000/11
using blood, urine or skin samples.
Academic Medical Center
Carrier testing

248 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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Laboratory Genetic Metabolic Diseases HMG-CoA lyase deficiency


(F0-132) hydroxymethylglutaric aciduria
Meibergdreef 9 HL deficiency
1105 AZ Amsterdam HMG
The Netherlands 3-OH 3-CH3 glutaric aciduria
Ph: +31 20 5662026 / 5393 3-OH 3-methyl glutaric aciduria
E-mail: gmz_enzym@amc.nl
Where can I find more information?
What is the cost of the confirmatory
Organic Acidemia Association
test?
http://www.oaanews.org
350 (+ 100 for fibroblast culturing)

Save Babies Through Screening


How many people have HMG lyase
Foundation
deficiency?
http://www.savebabies.org/
This condition is very rare. The actual
incidence is unknown. CLIMB (Children Living with Inherited
Metabolic Disorders)
Does HMG lyase deficiency happen
http://www.climb.org.uk
more frequently in a certain ethnic
group? Genetic Alliance
HMG lyase deficiency happens in all
http://www.geneticalliance.org/
ethnic groups throughout the world. It
happens more frequently in people
from Saudi Arabia, Portugal, and
Spain.

Does HMG lyase deficiency go by any


other names?

This condition is sometimes also


called:

249 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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I
Where can Confirmatory Testing
sobutyryl-CoA

be done for this condition?


Dehydrogenase What is the cost of the
confirmatory test?
Deficiency How many people have IBD
deficiency?
Disorder name: Isobutyryl-CoA
Does IBD deficiency happen more
dehydrogenase deficiency
often in a certain ethnic group?
Acronym: IBD deficiency
Does IBD deficiency go by any
other names?
What is IBD deficiency?
Where can I find more
What causes IBD deficiency?
information?
If IBD deficiency is not treated,
what problems occur?
This fact sheet contains general
What is the treatment for IBD
information about IBD deficiency.
deficiency?
Every child is different and some of
What happens when IBD
these facts may not apply to your child
deficiency is treated?
specifically. At present, little is known
What causes the isobutyryl-CoA
about IBD deficiency, and there is no
dehydrogenase enzyme to be
standard treatment plan. Certain
absent or not working correctly?
treatments may be recommended for
How is IBD deficiency inherited?
some children but not others. All
Is genetic testing available?
children with IBD deficiency should be
What other testing is available?
followed by a metabolic doctor in
Can you test during pregnancy?
addition to their primary doctor.
Can other members of the family
have IBD deficiency or be What is IBD deficiency?
carriers? IBD stands for isobutyryl-CoA
Can other family members be dehydrogenase. IBD deficiency has
tested? symptoms that are part of two different

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groups of conditions: organic acid


Organic Acid Disorders:
disorders and fatty acid oxidation
Organic acid disorders (OAs) are a
disorders. Some children with IBD
group of rare inherited conditions.
deficiency have problems breaking
They are caused by enzymes that do
down an amino acid called valine from
not work properly. A number of
the food they eat.
enzymes are needed to process
protein from the food we eat for use
by the body. Problems with one or
more of these enzymes can cause an
organic acid disorder.

People with organic acid disorders


cannot break down protein properly.
This causes harmful substances to
build up in their blood and urine.
These substances can affect health,
growth and learning.

The symptoms and treatment vary


between different organic acid
disorders. They can also vary from
person to person with the same
organic acid disorder. See the fact
sheets for each specific organic acid
disorder.

Organic acid disorders are inherited


in an autosomal recessive manner
and affect both males and females.

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In order for the body to use protein


Fatty Acid Disorders:
from the food we eat, it is broken down
Fatty acid oxidation disorders (FAODs)
into smaller parts called amino acids.
are a group of rare inherited conditions.
Special enzymes then make changes to
They are caused by enzymes that do not
the amino acids so the body can use
work properly.
them.
A number of enzymes are needed to
break down fats in the body (a process
called fatty acid oxidation). Problems IBD deficiency occurs when an
with any of these enzymes can cause a enzyme, called isobutyryl-CoA
fatty acid oxidation disorder. People with dehydrogenase, is either missing or
FAODs cannot properly break down fat not working properly. This enzymes
from either the food they eat or from fat job is to help break down valine. When
stored in their bodies. a child with IBD deficiency eats food
containing valine, harmful substances
The symptoms and treatment vary
build up in the blood and cause
between different FAODs. They can also
problems. Valine is found in all foods
vary from person to person with the same
that contain protein.
FAOD. See the fact sheets for each
specific FAOD. If IBD deficiency is not treated, what
problems occur?
FAODs are inherited in an autosomal
recessive manner and affect both males
and females.

What causes IBD deficiency?

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deficiency, symptoms began at one


year of age.

Symptoms included:
enlarged, weakened heart (called
cardiomyopathy)
anemia
poor growth
low carnitine levels (a substance
needed for the breakdown of
fatty acids)

What is the treatment for IBD


deficiency?
Your babys primary doctor will work
with a metabolic doctor and a dietician
experienced with IBD deficiency to

IBD deficiency is very rare and little is provide care for your child.

known about the effects. So far,


It is important to talk with a metabolic
symptoms have only been reported in a
doctor about possible treatment as
few children. Each child with IBD
soon as you know your child has IBD
deficiency is likely to have somewhat
deficiency. Certain treatments may be
different effects. Some children found
advised for some children but not
to have IBD deficiency during newborn
others. Some treatments may be
screening have never had symptoms.
needed throughout life.

It is likely that babies with IBD


The following are treatments that may
deficiency will be healthy at birth. In
be recommended for some babies and
the first child reported to have IBD
children with IBD deficiency:

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1. Medications Your metabolic doctor and dietician


Children with IBD deficiency may be will give you a feeding plan designed
helped by taking L-carnitine. This is a for your infants needs.
safe and natural substance that helps
2. Low-valine food plan (including
body cells make energy. It also helps
medical foods)
the body get rid of harmful wastes. L-
Most children with IBD deficiency
carnitine may help prevent or treat
seem to do fine without a change in
heart problems and anemia in children
diet. However, some children may be
with IBD deficiency. Do not use L-
advised to eat a diet made up of foods
carnitine without checking with your
low in valine. Valine is found in all
doctor. Unless you are advised
foods with protein.
otherwise, use only L-carnitine
prescribed by your doctor.
Foods high in protein that may need to
be limited include:
2. Avoid going a long time without
milk and dairy products
food
meat and poultry
Some infants and young children with
fish
IBD deficiency may be advised to eat
eggs
frequently to prevent health effects.
dried beans and legumes
Your metabolic doctor will tell you how
nuts and peanut butter
often your child needs to be fed. In
general, it is often suggested that There are medical foods such low-
infants be fed every four to six hours.
protein flours, pastas, rice, and special
Going without food for a long time
formulas that are made especially for
causes the body to use its stores of fat
people with organic acid disorders.
and protein for energy. In some people
Your dietician will let you know
with IBD deficiency, this may lead to whether you should use these foods to
the buildup of harmful substances in
supplement your childs diet.
the blood.

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Some states offer help with payment, or What causes the enzyme to be absent
require private insurance to pay for the or not working correctly?
formula and other special medical Genes tell the body to make various
foods. enzymes. People with IBD deficiency
have a pair of genes that do not work
If you are advised to change your
correctly. Because of the changes in
childs diet, it is important not to
this pair of genes, the isobutyryl-CoA
remove all protein from the diet.
dehydrogenase enzyme either does not
Children need a certain amount to grow
work properly or is not made at all.
properly. Your dietician will create a
food plan that contains the right
amount of protein, nutrients, and
How is IBD deficiency inherited?
energy to keep your child healthy.
IBD deficiency is inherited in an
What happens when IBD deficiency autosomal recessive manner. It affects
is treated? both boys and girls equally.
Although there is very little information Everyone has a pair of genes that make
available, it is thought that with prompt the isobutyryl-CoA dehydrogenase
and careful treatment, children with enzyme. In children with IBD
IBD deficiency will be able to live deficiency, neither of these genes
healthy lives with typical growth and works correctly. These children inherit
development. Treatment with carnitine one non-working gene for the condition
may reverse the heart problems and from each parent.
anemia and may improve growth.

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Parents of children with IBD deficiency deficiency. Talk with your genetic
rarely have the disorder. Instead, each counselor or metabolic doctor if you
parent has a single non-working gene have questions about DNA testing.
for IBD deficiency. They are called
DNA testing is not necessary to
carriers. Carriers do not have IBD
diagnose your child. If available, it can
deficiency because the other gene of
be helpful for carrier testing or prenatal
this pair is working correctly.
diagnosis, discussed below.
When both parents are carriers, there
What other testing is available?
is a 25% chance in each pregnancy for
Special tests on blood, urine, or skin
the child to have IBD deficiency. There
samples can be done to confirm IBD
is a 50% chance for the child to be a
deficiency. Talk to your metabolic
carrier, just like the parents. And, there
doctor or genetic counselor if you have
is a 25% chance for the child to have
questions about testing for IBD
two working genes.
deficiency.
Genetic counseling is available to
families who have children with IBD
deficiency. Genetic counselors can
answer your questions about how IBD
deficiency is inherited, choices during
future pregnancies, and how to test
other family members. Ask your doctor
about a referral to a genetic counselor.

Is genetic testing available?

Genetic testing for IBD deficiency is


available. Genetic testing, also called
DNA testing, looks for changes in the
pair of genes that causes IBD

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Can you test during pregnancy? children in the family have this
If both gene changes have been found condition is important because early
in your child with IBD deficiency, DNA treatment may prevent serious health
testing can be done during future problems. Talk to your metabolic
pregnancies. The sample needed for doctor or genetic counselor about
this test is obtained by either CVS or testing your other children.
amniocentesis.
IBD deficiency carriers
It may also be possible to do an
Brothers and sisters who do not have
enzyme test using cells from the fetus.
IBD deficiency still have a chance to be
The sample needed for this test is
carriers like their parents. Except in
obtained by either CVS or
special cases, carrier testing should
amniocentesis.
only be done in people over 18 years of
age.
Parents may either choose to have
testing during pregnancy or wait until
Each of the parents brothers and
birth to have the baby tested. A genetic
sisters has a 50% chance to be a
counselor can talk to you about your
carrier. It is important for other family
choices and answer questions about
members to be told that they could be
prenatal testing or testing your baby
carriers. There is a small chance they
after birth.
are also at risk to have children with
IBD deficiency.
Can other members of the family
have IBD deficiency or be carriers?
Some states do not provide newborn
screening for IBD deficiency. However,
Having IBD deficiency
expanded newborn screening through
The brothers and sisters of a baby with private labs is available for babies born
IBD deficiency have a small chance of in states that do not screen for this
being affected, even if they havent had condition.
symptoms. Finding out whether other

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When both parents are IBD carriers, diagnosis is done by Gas


newborn screening results are not Chromatography Mass Spectrometry
sufficient to rule out the condition in a (GC/MS) using urine sample
newborn baby. In this case, special
diagnostic testing should be done in
addition to newborn screening. Center
PreventiNe Lifecare Pvt. Ltd.
Can other family members be tested?
RPT House, Plot No. 6, Sector 24,

Diagnostic testing Turbhe, Navi Mumbai 400705

To make sure they do not have the Ph: 022-61980000/11

condition, brothers and sisters of a


How many people have IBD
child with IBD deficiency can be tested
deficiency?
using blood, urine or skin samples.
IBD deficiency is very rare. Less than

Carrier testing 30 people have been reported in the

If both gene changes have been found medical literature, and most people

in the child with IBD deficiency, other with IBD have no symptoms. The

family members can have DNA testing actual incidence is unknown.

to see if they are carriers.


Does IBD deficiency happen more

If DNA testing is not possible or would frequently in a certain ethnic group?

not be helpful, other methods of carrier IBD deficiency does not happen more

testing may be available. Your often in any specific race, ethnic group,

metabolic doctor or genetic counselor geographical area or country.

can answer your questions about


Does IBD deficiency go by any other
carrier testing.
names?

Where can Confirmatory Testing be IBD deficiency is sometimes also

done for this condition? called:

The confirmatory test for the

258 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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Acyl-CoA dehydrogenase family,


member 8
ACAD8 deficiency

Where can I find more information?


Organic Acidemia Association
http://www.oaanews.org

CLIMB (Children Living with Inherited


Metabolic Disorders)
http://www.climb.org.uk

Genetic Alliance
http://www.geneticalliance.org/

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I
What is the cost of the
sovaleric Acidemia

confirmatory test?
How many people have IVA?
Does IVA happen more often in a
Disorder name: Isovaleric Acidemia certain ethnic group?
Acronym: IVA Does IVA go by any other names?
Where can I find more
What is IVA?
information?
What causes IVA?
If IVA is not treated, what This fact sheet contains general
problems occur? information about IVA. Every child is
What is the treatment for IVA? different and some of these facts may
What happens when IVA is not apply to your child specifically.
treated? Certain treatments may be
What causes the Isovaleryl-CoA recommended for some children but
dehydrogenase enzyme to be not others. All children with IVA
absent or not working correctly? should be followed by a metabolic
How is IVA inherited? doctor in addition to their primary
Is genetic testing available? doctor.
What other testing is available?
What is IVA?
Can you test during pregnancy?
IVA stands for isovaleric acidemia. It
Can other members of the family
is one type of organic acid disorder.
have IVA or be carriers?
People with IVA have problems
Can other family members be
breaking down an amino acid called
tested?
leucine from the food they eat.
Where can Confirmatory Testing
be done for this condition?

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What causes IVA? the amino acids so the body can use
In order for the body to use protein them.
from the food we eat, it is broken down
IVA occurs when an enzyme, called
into smaller parts called amino acids.
isovaleryl-CoA dehydrogenase, is
Special enzymes then make changes to
either missing or not working properly.

Organic Acid Disorders: This enzymes job is to help break


Organic acid disorders (OAs) are a down a substance called isovaleryl-

group of rare inherited conditions. They CoA. It is made in the body when the

are caused by enzymes that do not work amino acid leucine is broken down.

properly. A number of enzymes are When a child with IVA eats food

needed to process protein from the food containing leucine, a substance called
we eat for use by the body. Problems isovaleric acid builds up in the blood

with one or more of these enzymes can and causes problems. Leucine is found

cause an organic acid disorder. in all foods that contain protein.

People with organic acid disorders


cannot break down protein properly.
This causes harmful substances to
build up in their blood and urine. These
substances can affect health, growth
and learning.

The symptoms and treatment vary


between different organic acid
disorders. They can also vary from
person to person with the same organic
acid disorder. See the fact sheets for
each specific organic acid disorder.

Organic acid disorders are inherited in


an autosomal recessive manner and
NEWBORN SCREENING- SCREEN EARLY TREAT EARLY
261both males and females.
affect
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Babies with IVA seem healthy at birth.


Often, the first symptoms start between
one day and two weeks of age.

IVA causes episodes of illness called


metabolic crises. Some of the first
symptoms of a metabolic crisis are:

poor appetite
extreme sleepiness or lack of
energy
vomiting
problems staying warm
an odor similar to sweaty feet

Other symptoms can then follow:


increased levels of acidic
substances in the blood, called
If IVA is not treated, what problems metabolic acidosis
occur? high levels of ammonia in the
The effects of IVA vary from person to blood
person. There are two main forms of ketones in the urine
the condition. About half of all babies low platelets
start showing symptoms shortly after low level of white blood cells
birth. The other form, called chronic- seizures
intermittent, starts later in infancy or swelling of the brain
childhood. bleeding in the brain
coma, sometimes leading to
IVA in babies
death

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If not treated, many babies die during Your babys primary doctor will work
their first metabolic crisis. In those who with a metabolic doctor and a dietician
survive, repeated episodes of metabolic experienced with IVA to care for your
crisis can cause brain damage. This child.
can result in life-long learning
Prompt treatment is needed to prevent
problems or mental retardation.
metabolic crises and the health effects
Chronic/intermittent IVA that follow. You should start treatment
Symptoms often start around one year as soon as you know your child has
of age. Some children, though, do not IVA. Certain treatments may be
have symptoms until later in childhood. advised for some children but not
others. Treatment is usually needed
Episodes of metabolic crisis can be
throughout life.
brought on by illness, infection, or by
eating large amounts of protein. When The following are treatments often
a child is ill, body protein is broken recommended for babies and children
down for energy. In a child with IVA, with IVA:
this can cause high levels of isovaleric
1. Low-leucine diet, medical foods
acid and results in a metabolic crisis.
and formula
Between episodes of metabolic crisis, Most children need to eat a diet made
children with IVA are usually healthy. up of foods low in leucine. Special
medical foods and a leucine-free
Some people have very mild or no
formula are usually part of the diet.
symptoms and are only found to be
Your dietician will create a food plan
affected after a brother or sister is
that contains the right amount of
diagnosed. Newborn screening also
protein, nutrients, and energy to keep
identifies infants that may never
your child healthy. A special food plan
develop serious symptoms.
should be continued throughout life.

What is the treatment for IVA?


Low-leucine / low-protein diet

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Foods high in protein (and leucine) that In addition to a low-protein diet, many
may need to be avoided or limited children are given a special leucine-free
include: medical formula. Your metabolic doctor
milk and dairy products and dietician will decide whether your
meat and poultry child needs this formula. Some states
fish offer help with payment, or require
eggs private insurance to pay for the formula
dried beans and legumes and other special medical foods.
nuts and peanut butter
2. Medications
Eating large amounts of these foods
Glycine is an amino acid that helps the
can cause isovaleric acid levels to rise,
body get rid of isovaleric acid. It is
causing illness.
often given as a supplement to children
Many vegetables and fruits have only with IVA. It may help prevent
small amounts of protein and can be metabolic crises. Your doctor will tell
eaten in carefully measured amounts. you whether your child needs glycine
and how much to use.
Do not remove all protein from the diet.
Children with IVA need a certain Some children may benefit by taking L-
amount to grow properly. Any diet carnitine. This is a safe and natural
changes should be under the guidance substance that helps body cells make
of a dietician. energy. It also helps the body get rid of
isovaleric acid and other harmful
Medical foods and formula
wastes. Your doctor will decide
There are medical foods such as
whether or not your child needs L-
special low-protein flours, pastas, and
carnitine. Unless you are advised
rice that are made especially for people
otherwise, use only L-carnitine
with organic acid disorders. Your
prescribed by your doctor.
dietician will tell you how to use these
Do not use any medication or
foods to supplement your childs diet.

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supplement without checking with your metabolic crisis. In addition, they need
metabolic doctor. to avoid eating protein when they are
ill.
Children with symptoms of a metabolic
crisis need medical treatment right Children who are sick often dont want
away. They may need to be treated in to eat. If they cant eat, or if they show
the hospital. During a metabolic crisis, signs of a metabolic crisis, they may
children may be given bicarbonate, need to be treated in the hospital. Ask
glucose, and other medications by IV to your metabolic doctor if you should
help reduce the acid levels in the carry a special travel letter with
blood. medical instructions for your childs
care.
3. Call your doctor at the start of any
illness What happens when IVA is treated?
In some children, even minor illnesses With prompt and careful treatment,
such as a cold or the flu can lead to a children with IVA have a good chance
metabolic crisis. In order to prevent to live healthy lives with typical growth
problems, call your doctor right away and development.
when your child has any of the
Even when treated, some children still
following:
have repeated bouts of metabolic
loss of appetite crisis. This can lead to life-long
vomiting learning problems or mental
diarrhea retardation. As they get older, children
infection or illness tend to have fewer metabolic crises.
fever
What causes the isovaleryl-CoA
Children with IVA need to eat more dehydrogenase enzyme to be absent
carbohydrates and drink more fluids or not working correctly?
when they are ill even if theyre not Genes tell the body to make various
hungry or they could have a enzymes. People with IVA have a pair

265 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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of genes that do not work correctly. chance for the child to have two
Because of the changes in this pair of working genes.
genes, the isovaleryl-CoA
Genetic counseling is available to
dehydrogenase enzyme either does not
families who have children with IVA.
work properly or is not made at all.
Genetic counselors can answer your
How is IVA inherited? questions about how the condition is
IVA is inherited in an autosomal inherited, choices during future
recessive manner. It affects both boys pregnancies, and how to test other
and girls equally. family members. Ask your doctor about
a referral to a genetic counselor.
Everyone has a pair of genes that make
the isovaleryl-CoA dehydrogenase Is genetic testing available?
enzyme. In children with IVA, neither Genetic testing for IVA can be done on
of these genes works correctly. These
children inherit one non-working gene
for the condition from each parent.

Parents of children with IVA rarely


have the condition themselves. Instead,
each parent has a single non-working
gene for IVA. They are called carriers.
Carriers do not have IVA because the
other gene of this pair is working
correctly.

When both parents are carriers, there


is a 25% chance in each pregnancy for
the child to have IVA. There is a 50%
chance for the child to be a carrier, just
like the parents. And, there is a 25%

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a blood sample. Genetic testing, also Parents may choose to have testing
called DNA testing, looks for changes during pregnancy or wait until birth to
in the pair of genes that causes IVA. If have the baby tested. A genetic
you have questions about DNA testing, counselor can talk to you about your
talk with your genetic counselor or choices and answer questions about
metabolic doctor. prenatal testing or testing your baby
after birth.
DNA testing is not necessary to
diagnose your child. However, it can be Can other members of the family
helpful for carrier testing or prenatal have IVA or be carriers?
diagnosis, discussed below.
Having IVA
What other testing is available? The brothers and sisters of a baby with
Special tests on blood, urine, or skin IVA may have a small chance of being
samples can be done to confirm IVA. affected, even if they havent had
Talk to your metabolic doctor or symptoms. Finding out whether other
genetic counselor if you have questions children in the family have this
about testing. condition is important because early
treatment may prevent serious health
Can you test during pregnancy?
problems. Talk to your metabolic
If both gene changes have been found
doctor or genetic counselor about
in your child, DNA testing can be done
testing your other children.
during future pregnancies. The sample
IVA carriers
needed for this test is obtained by
Brothers and sisters who do not have
either CVS or amniocentesis.
IVA still have a chance to be carriers
like their parents. Except in special
If DNA testing would not be helpful, an
cases, carrier testing should only be
enzyme test using cells from the fetus
done in people over 18 years of age.
can be done during pregnancy. The
sample needed for this test is obtained
Each of the parents brothers and
by either CVS or amniocentesis.
sisters has a 50% chance to be a

267 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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carrier. It is important for other family can answer your questions about
members to be told that they could be carrier testing.
carriers. There is a small chance they
Where can Confirmatory Testing be
are also at risk to have children with
done for this condition?
IVA.

The confirmatory test for the


All states offer newborn screening for
diagnosis is done by Gas
IVA. However, when both parents are
Chromatography Mass Spectrometry
carriers, newborn screening results are
(GC/MS) using urine sample.
not sufficient to rule out the condition
in a newborn baby. In this case, special Center
diagnostic testing should be done in PreventiNe Lifecare Pvt. Ltd.
addition to newborn screening. RPT House, Plot No. 6, Sector 24,
Turbhe, Navi Mumbai 400705
Can other family members be tested?
Ph: 022-61980000/11
Diagnostic testing
How many people have IVA?
Brothers and sisters of a child with IVA
About one in every 230,000 babies in
can be tested using blood, urine or skin
the United States is born with IVA.
samples.

Does IVA happen more frequently in


Carrier testing
a certain ethnic group?
If both gene changes have been found
IVA does not happen more often in any
in your child, other family members
specific race, ethnic group,
can have DNA testing to see if they are
geographical area or country.
carriers.

Does IVA go by any other names?


If DNA testing is not possible or would
IVA is sometimes also called:
not be helpful, other methods of carrier
isovaleric Acid CoA
testing may be available. Your
Dehydrogenase Deficiency
metabolic doctor or genetic counselor
IVD deficiency

268 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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isovaleryl CoA carboxylase


deficiency

Where can I find more information?


Organic Acidemia Association
http://www.oaanews.org

Save Babies Through Screening


Foundation
http://www.savebabies.org/

CLIMB (Children Living with Inherited


Metabolic Disorders)
http://www.climb.org.uk

Genetic Alliance
http://www.geneticalliance.org/

Isovaleric Acidemia: A Guide for


Parents (PacNoRGG publication)
http://www.westernstatesgenetics.org/
pacnorgg/PDFs_all-
081409/isovaleric_eng.pdf

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What is the cost of the


confirmatory test?

M ethylmalonic
Acidemia


How many people have MMA?
Does MMA happen more often in
a certain ethnic group?
Does MMA go by any other
Disorder name: Methylmalonic
names?
Acidemia
Where can I find more
Acronym: MMA
information?

What is MMA?
This fact sheet contains general
What causes MMA?
information about MMA. Every child is
If MMA is not treated, what
different and some of these facts may
problems occur?
not apply to your child specifically.
What is the treatment for MMA?
Certain treatments may be
What happens when MMA is
recommended for some children but
treated?
not others. All children with MMA
What causes the enzyme to be
should be followed by a metabolic
absent or not working correctly?
doctor in addition to their primary care
How is MMA inherited?
provider.
Is genetic testing available?
What other testing is available? What is MMA?
Can you test during pregnancy? MMA stands for methylmalonic
Can other members of the family acidemia. It is one type of organic acid
have MMA or be carriers? disorder. People with MMA have
Can other family members be problems breaking down and using
tested? certain amino acids and fatty acids
Where can Confirmatory Testing from the food they eat.
be done for this condition?
What causes MMA?

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In order for the body to use protein the amino acids so the body can use
from the food we eat, it is broken down them. In the same way, fat from the
into smaller parts called amino acids. food we eat is broken down by
Special enzymes then make changes to enzymes into fatty acids that the body
can use for energy.
Organic Acid Disorders:
Organic acid disorders (OAs) are a MMA occurs when one of these special

group of rare inherited conditions. enzymes is either missing or not

They are caused by enzymes that do working properly. Without this enzyme,

not work properly. A number of certain amino acids and fatty acids

enzymes are needed to process cannot be used correctly. This causes

protein from the food we eat for use by glycine, methylmalonic acid, and other

the body. Problems with one or more harmful substances to build up in the

of these enzymes can cause an blood and urine and cause health

organic acid disorder. problems.

People with organic acid disorders There are a number of different forms

cannot break down protein properly. of MMA. Some forms can be treated

This causes harmful substances to with vitamin B12 injections. These

build up in their blood and urine. types are called vitamin B12

These substances can affect health, responsive. Two types of MMA that

growth and learning. often can be treated with vitamin B12


are Cobalamin A (CblA) deficiency and
The symptoms and treatment vary Cobalamin B (CblB) deficiency.
between different organic acid
disorders. They can also vary from There are other forms of MMA which

person to person with the same cannot be treated with vitamin B12.

organic acid disorder. See the fact These types are called vitamin B12

sheets for each specific organic acid non-responsive. One of these is called

disorder. Mut 0. It is caused by the absence of


an enzyme called methylmalonyl-CoA
Organic acid disorders are inherited
271 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY
in an autosomal recessive manner
Unauthorised reproduction of this article is prohibited
and affect both males and females.
BABYSHIELD TMS FACT SHEET

with MMA. These amino acids are


found in all foods that contain protein.
Large amounts are found in meat, eggs,
milk, and other dairy products. Smaller
amounts are found in flour, cereal, and
some vegetables and fruits.

If MMA is not treated, what problems


occur?
Each child with MMA is likely to have
somewhat different effects. Many
babies with MMA start having
symptoms in the first few days of life.
Others begin to show symptoms
sometime in infancy or childhood.
Some people with MMA may never
mutase (MCM). Another type of MMA develop symptoms.
that does not respond to vitamin B12
MMA causes episodes of illness called
treatment is called Mut . People with
the Mut type of MMA have too little metabolic crises. Some of the first

of the MCM enzyme. symptoms of a metabolic crisis are:


poor appetite
Another form of MMA, called MMA vomiting
with homocystinuria, is described in a extreme sleepiness or lack of
separate fact sheet. See the fact sheet energy
MMA+HCU for more information about low muscle tone (floppy muscles
this condition. and joints)

Isoleucine, valine, methionine, and Common blood and urine findings are:
threonine are the four amino acids that ketones in the urine
cannot be used correctly by people

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high levels of acidic substances However, some continue to have


in the blood, called metabolic problems with health and development.
acidosis Some children have long-term
high blood ammonia levels problems even if they have never had a
high blood and urine levels of metabolic crisis. These can include:
glycine learning disabilities or mental
high blood and urine levels of retardation
methylmalonic acid and delays in walking and motor
propionic acid skills
high levels of other harmful abnormal involuntary
substances movements (dystonia and
low platelets chorea)
low white blood cells rigid muscle tone, called
anemia spasticity
poor growth with short stature
If a metabolic crisis is not treated, a
skin rashes and infections
child with MMA can develop:
osteoporosis
breathing problems
enlarged liver
seizures
kidney disease or failure
stroke
vision loss due to problems with
coma, sometimes leading to
the nerves in the eye
death
Without treatment, brain and nerve
A metabolic crisis can be triggered by:
damage can occur. This can cause
eating large amounts of protein
mental retardation and problems with
illness or infection
involuntary movements. Death is
going too long without food
common in untreated babies and
stressful events such as surgery
children.

Between episodes of metabolic crisis,


children with MMA may be healthy.

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A small number of people with MMA Over 90% of children with CblA
never show symptoms. deficiency respond to vitamin B12
injections. About 40% of children with
What is the treatment for MMA?
CblB deficiency are helped by this
Your babys primary doctor will work
treatment. Your doctors may need to
with a metabolic doctor and a dietician
treat your child with vitamin B12 for
familiar with MMA to care for your
short period of time to determine
child.
whether this treatment is useful.

Prompt treatment is needed to reduce


Children with MMA may benefit by
the chance for mental retardation and
taking L-carnitine. This is a safe and
serious medical problems. Children
natural substance that helps the body
with vitamin B12 responsive MMA are
make energy. It also helps get rid of
given vitamin B12. In addition, most
harmful wastes. Your doctor will
children need to be on a low-protein
decide whether or not your child needs
diet and drink a special medical
L-carnitine. Unless you are advised
formula. You should start the
otherwise, use only L-carnitine
treatments as soon as you know your
prescribed by your doctor.
child has MMA.
Antibiotics taken by mouth can help
The following are treatments often
lower the amount of methylmalonic
recommended for children with MMA:
acid made in the intestines. Your
doctor will decide if your child needs
1. Medication
antibiotics and, if so, what type.
The main treatment for vitamin B12
responsive MMA is vitamin B12
Children who are having symptoms of
injections in the form of
a metabolic crisis should be treated in
hydroxocobalamin (OH-cbl) or
the hospital. During a metabolic crisis,
cyanocobalamin (CN-cbl). Vitamin B12
your child may be given medications
injections can prevent symptoms in
such as bicarbonate through an IV to
children with this form of MMA.
help reduce the acid levels in the blood.

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Glucose is given by IV to prevent the Many vegetables and fruits have only
breakdown of protein and fat stored in small amounts of protein and can be
the body. eaten in carefully measured amounts.
Do not remove all protein from the diet.
Do not use any medication without
Children with MMA need a certain
checking with your doctor.
amount to grow properly.

2. Low-protein diet, medical foods


Your dietician can create a food plan
and medical formula
that contains the right amount of
Low-protein diet
protein, nutrients, and energy to keep
A food plan low in the amino acids
your child healthy. It is likely your child
leucine, valine, methionine, and
will need to be on a special food plan
threonine with limited amounts of
throughout life.
protein is often recommended. Most
food in the diet will be carbohydrates Medical formula and foods
(bread, cereal, pasta, fruit, vegetables, In addition to a low-protein diet, your
etc.). Carbohydrates give the body child may be given a special medical
many types of sugar that can be used formula. This formula contains the
as energy. Eating a diet high in correct amount of protein and nutrients
carbohydrates and low in protein and your child needs for normal growth and
fat can help prevent metabolic crises. development. Your metabolic doctor
and dietician will tell you what type of
Foods high in protein that may need to
formula is best and how much to use.
be avoided or limited include:
milk and dairy products There are also medical foods such as
meat and poultry special low-protein flours, pastas, and
fish rice that are made especially for people
eggs with organic acid disorders. Your
dried beans and legumes dietician will tell you how to use these
nuts and peanut butter foods as part of your childs diet.

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Some states offer help with payment or Tracking of ketones


require private insurance to pay for the Periodic urine tests to check the level
formula and other special medical of ketones can be done at home or at
foods. the doctors office. Ketones are
substances formed when body fat is
3. Avoid going a long time without
broken down for energy. This happens
food
after going without food for long
Infants and young children with MMA
periods of time, during illness, and
need to eat frequently to prevent a
during periods of heavy exercise. Too
metabolic crisis. Your metabolic doctor
many ketones in the urine may signal
will tell you how often your child needs
the start of a metabolic crisis.
to be fed. In general, it is often
suggested that infants be fed every four
Blood tests
to six hours. Some babies need to eat
Your child will have regular blood tests
even more frequently than this. It is
to measure the level of amino acids.
important that infants be fed during the
Urine tests may also be done. Your
night. They may need to be woken up
childs diet and medication may need to
to eat if they do not wake up on their
be adjusted based on the results of
own. Your metabolic doctor and
these tests.
dietician will give you an appropriate
feeding plan for your infant. Your 5. Call your doctor at the start of any
doctor will also give you a sick day illness
plan, tailored to your childs needs, for For children with MMA, even minor
you to follow during illnesses or other illness could lead to a metabolic crisis.
times when your child will not eat. To prevent serious health problems,
call your doctor right away when your
Your metabolic doctor will continue to
child has any of the following:
advise you on how often your child
should eat as he or she gets older. loss of appetite
vomiting
4. Regular blood and urine tests

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diarrhea and development. In general, the earlier


infection or illness treatment is started, the better the
fever outcome.

When ill, your child needs extra fluids Children who respond to vitamin B12
and carbohydrates in order to prevent a treatment tend to do very well as long
metabolic crisis. During an illness, you as treatment is continued. Children
should restrict protein and give your who are not treated until after they
child starchy foods and fluids. Children have symptoms may have lasting
with MMA may need to be treated in health and learning problems.
the hospital during illness to avoid
Even with treatment, some children
serious health problems. Ask your
develop life-long learning disabilities or
metabolic doctor if you should carry a
mental retardation. In addition, despite
special travel letter with medical
treatment, seizures, involuntary
instructions for your childs care.
movement disorders, and kidney failure
6. Organ transplantation have occurred in some children.
Some children with MMA are given
What causes the enzyme to be absent
liver or kidney transplants, or both.
or not working correctly?
This may reduce some of the
Genes tell the body to make various
symptoms. However, transplant
enzymes. People with MMA have a pair
surgery has serious risks and may or
of genes that do not work correctly.
may not be right for your child. Talk
Because of these gene changes, an
with your doctor or metabolic specialist
enzyme needed by the body does not
if you have questions about the risks
work properly or is not made at all.
and benefits of transplantation.

How is MMA inherited?


What happens when MMA is treated?
MMA is inherited in an autosomal
Babies and children who have prompt
recessive manner. It affects both boys
and ongoing treatment may be able to
and girls equally.
live healthy lives with normal growth

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Everyone has a pair of genes that make


the needed enzyme. In children with
MMA, neither of these genes works
correctly. These children inherit one
non-working gene for the condition
from each parent.

Parents of children with MMA rarely


have the disorder. Instead, each parent
has a single non-working gene for
MMA. They are called carriers. Carriers
do not have MMA because the other
gene of this pair is working correctly.

When both parents are carriers, there


is a 25% chance in each pregnancy for
the child to have MMA. There is a 50% Genetic counseling is available to
chance for the child to be a carrier, just
families who have children with MMA.
like the parents. And, there is a 25%
Genetic counselors can answer your
chance for the child to have two questions about how MMA is inherited,
working genes. choices during future pregnancies, and
how to test other family members. Ask
your doctor about a referral to a genetic
counselor.

Is genetic testing available?

Genetic testing is available for MMA.


Genetic testing, also called DNA
testing, looks for changes in the pair of
genes that cause MMA. Talk with your

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genetic counselor or metabolic doctor if Parents may either choose to having


you have questions about DNA testing. testing during pregnancy or wait until
birth to have the baby tested. A genetic
DNA testing is not necessary to
counselor can talk to you about your
diagnose your child. However, if
choices and answer questions about
available, it can be helpful for carrier
prenatal testing or testing your baby
testing or prenatal diagnosis,
after birth.
discussed below.
Can other members of the family
What other testing is available?
have MMA or be carriers?
Special tests on blood, urine, or skin
samples can be done to help confirm Having MMA
MMA. Talk to your metabolic doctor or If they are healthy and growing
genetic counselor if you have questions normally, older brothers and sisters of
about testing for MMA. a baby with MMA are unlikely to have
the condition. However, finding out if
Can you test during pregnancy?
other children in the family have this
If both gene changes have been found
condition is important because early
in your child with MMA, DNA testing
treatment can prevent serious health
can be done during future pregnancies.
problems. Ask your metabolic doctor
The sample needed for this test is
whether your other children should be
obtained by either CVS or
tested.
amniocentesis.
MMA carriers
If DNA testing would not be helpful,
Brothers and sisters who do not have
MMA can also be detected by an
MMA still have a chance to be carriers
enzyme test using cells from the fetus.
like their parents. Except in special
The sample needed for this test is
cases, carrier testing should only be
obtained by amniocentesis.
done on people over 18 years of age.

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Each of the parents brothers and about carrier testing, ask your genetic
sisters has a 50% chance to be an counselor or metabolic doctor.
MMA carrier. It is important for other
Where can Confirmatory Testing be
family members to be told that they
done for this condition?
could be carriers. There is a small
The confirmatory testing for the
chance they are also at risk to have
disorder is done after B12
children with MMA.
supplementation and serial urine
All states provide newborn screening MMA estimation by GC/MS.
for MMA. However, when both parents
Center
are MMA carriers, newborn screening
PreventiNe Lifecare Pvt. Ltd.
results are not sufficient to rule out the
RPT House, Plot No. 6, Sector 24,
condition in a newborn baby. In this
Turbhe, Navi Mumbai 400705
case, special diagnostic testing should
Ph: 022-61980000/11
be done in addition to newborn
screening. . How many people have MMA?
About one in 80,000 babies in the
Can other family members be tested?
United States is born with MMA.

Diagnostic testing
Does MMA happen more frequently
Brothers and sisters of a child with
in a certain ethnic group?
MMA can have special tests on blood,
MMA occurs in all ethnic groups
urine, or skin samples. Talk to your
around the world. It does not occur
doctor or genetic counselor if you have
more often in any specific race, ethnic
questions about testing for MMA.
group, geographical area, or country.
Carrier testing
Does MMA go by any other names?
If the gene changes have been
There are a number of different forms
identified in your child with MMA,
of MMA. The vitamin B12 non-
carrier testing can be done for other
family members. If you have questions

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responsive forms are sometimes also CLIMB (Children Living with Inherited
called: Metabolic Disorders)
Methylmalonic aciduria due to http://www.climb.org.uk
methylmalonic CoA mutase
Save Babies Through Screening
deficiency
Foundation
Complementation group Mut
http://www.savebabies.org/
(includes Mut0 and Mut-)
Methylmalonyl CoA mutase
Genetic Alliance
deficiency
http://www.geneticalliance.org/
MCM Deficiency

The vitamin B12 responsive forms are


sometimes also called:
Methylmalonic aciduria, cblA
type
Methylmalonic aciduria, cblB
type
MMAA/MMAB
Adenosylcobalamin deficiency

Another type of MMA has additional


symptoms of a separate condition
called homocystinuria. See the fact
sheet MMA+HCU for more information
about this type of MMA.

Where can I find more information?


Organic Acidemia Association
http://www.oaanews.org

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M
Can other family members be
ethylmalonic

tested?
Acidemia with Where can Confirmatory Testing
be done for this condition?
Homocystinuri What is the cost of the
confirmatory test?
a
How many people have
MMA+HCU?
Disorder name: Methylmalonic
Does MMA+HCU happen more
Acidemia with Homocystinuria
often in a certain ethnic group?
Acronym: There is no standard
Does MMA+HCU go by any other
acronym for this condition.For this fact
names?
sheet we will use MMA+HCU
Where can I find more
What is MMA+HCU? information?
What causes MMA+HCU?
This fact sheet contains general
If MMA+HCU is not treated, what
information about methylmalonic
problems occur?
acidemia with homocystinuria
What is the treatment for
(MMA+HCU). Every child is different
MMA+HCU?
and some of these facts may not apply
What happens when MMA+HCU
to your child specifically. Certain
is treated?
treatments may be recommended for
What causes the enzyme to be
some children but not others. All
absent or not working correctly?
children with MMA+HCU should be
How is MMA+HCU inherited?
followed by a metabolic doctor in
Is genetic testing available?
addition to their primary care provider.
What other testing is available?
Can you test during pregnancy?
What is MMA+HCU?
Can other members of the family
MMA+HCU stands for methylmalonic
have MMA+HCU or be carriers?
acidemia with homocystinuria. It is

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one type of organic acid disorder. food they eat.


People with MMA+HCU have problems
breaking down and using certain
amino acids and fatty acids from the

Organic Acid Disorders:


Organic acid disorders (OAs) are a
group of rare inherited conditions.
They are caused by enzymes that do
not work properly. A number of
enzymes are needed to process
protein from the food we eat for use by
the body. Problems with one or more
of these enzymes can cause an
organic acid disorder.

People with organic acid disorders


cannot break down protein properly.
This causes harmful substances to
build up in their blood and urine.
What causes MMA+HCU?
These substances can affect health,
In order for the body to use protein
growth and learning.
from the food we eat, it is broken down

The symptoms and treatment vary into smaller parts called amino acids.

between different organic acid Special enzymes then make changes to

disorders. They can also vary from the amino acids so the body can use

person to person with the same them. In the same way, fat from the

organic acid disorder. See the fact food we eat is broken down into fatty

sheets for each specific organic acid acids that the body can use for energy.

disorder.

Organic acid disorders are inherited


NEWBORN SCREENING- SCREEN EARLY TREAT EARLY
in 283
an autosomal recessive manner
Unauthorised reproduction of this article is prohibited
and affect both males and females.
BABYSHIELD TMS FACT SHEET

MMA+HCU occurs when one of these amounts are found in flour, cereal, and
special enzymes is either missing or some vegetables and fruits.
not working properly. The job of these
If MMA+HCU is not treated, what
enzymes is to change vitamin B12 (also
problems occur?
called cobalamin) into a form that the
Each child with MMA+HCU is likely to
body can use. When the body is not
have somewhat different effects:
able to use vitamin B12 correctly, it
causes homocystine, methylmalonic
Most babies with CblC
acid and other harmful substances to
deficiency have shown
build up in the blood. This can lead to
symptoms within the first year,
serious health problems.
often by one month of age. A
small number of children with
There are a number of forms of
CblC deficiency have not had
MMA+HCU. The most common form is
symptoms until after 4 years of
called Cobalamin C deficiency (CblC).
age. A small number of
Rarer forms include Cobalamin D
individuals have been reported
deficiency (CblD) and Cobalamin F
to have developed their first
deficiency (CblF).
symptoms in their teens or early
There are other forms of MMA that twenties.
occur without homocystinuria. These Babies with CblF deficiency
are described in a separate fact sheet - usually have their first
see MMA. symptoms shortly after birth.
Children with CblD deficiency
Isoleucine, valine, methionine, and
usually show initial symptoms
threonine are the four amino acids that
later in childhood.
cannot be used correctly by people
with MMA+HCU. They are found in all It is possible that a small number of
foods that contain protein. Large people with this condition never
amounts are found in meat, eggs, milk, develop symptoms.
and other dairy products. Smaller

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Early-onset MMA+HCU anemia


In babies who have symptoms, low platelets
common findings are: low white blood cells
poor appetite excess clotting of the blood
poor growth
If not treated, metabolic acidosis can
extreme sleepiness or lack of
cause:
energy
breathing problems
low muscle tone (floppy muscles
seizures
and joints)
swelling of the brain
seizures
stroke
small head and brain size, called
coma, sometimes leading to
microcephaly
death
water on the brain, called
hydrocephalus
Metabolic acidosis and other
other brain abnormalities
symptoms can be triggered by:
delays in learning or mental
eating large amounts of protein
retardation illness or infection
vision problems
going too long without food
heart problems
stressful events such as surgery
kidney problems
skin rashes Later-onset MMA+HCU
Children who do not have symptoms
Lab findings can include:
until later in childhood often have some
high levels of homocysteine and
or all of the following symptoms:
methylmalonic acid in the blood
sudden loss of mental skills
and urine
forgetfulness and confusion
high levels of acidic substances episodes of psychosis or
in the blood, called metabolic
delirium
acidosis
behavior problems
protein or blood in the urine
tremor

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numbness or weakness in the The following are treatments often


limbs recommended for children with
unsteady gait MMA+HCU:
slurred speech
1. Low-protein diet, medical foods
blood clots
and medical formula
anemia, low platelets, and/or low
Low-protein diet
white blood cells
A food plan low in the amino acids
vision problems
leucine, valine, methionine, and
kidney problems
threonine with limited amounts of
What is the treatment for protein is often recommended. Most
MMA+HCU? food in the diet will be carbohydrates
Your babys primary doctor will work (bread, cereal, pasta, fruit, vegetables,
with a metabolic doctor and a dietician etc.). Carbohydrates give the body
familiar with MMA+HCU to care for many types of sugar that can be used
your child. as energy. Eating a diet high in
carbohydrates and low in protein and
It is not known how effective treatment
fat can help prevent metabolic crises.
is in preventing effects of MMA+HCU.
However, prompt and ongoing Foods high in protein that may need to
treatment may lessen the chance for be avoided or limited include:
mental retardation, psychiatric milk and dairy products
disorders, and serious health problems. meat and poultry
fish
Most children need to be on a low-
eggs
protein diet and drink a special medical
dried beans and legumes
formula. Many children are given
nuts and peanut butter
injections of vitamin B12. It is
important to start treatment as soon as Many vegetables and fruits have only
you know your child has MMA+HCU. small amounts of protein and can be
eaten in carefully measured amounts.

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Do not remove all protein from the diet. formula and other special medical
Children with MMA+HCU need a foods.
certain amount to grow properly.
2. Medication
Your dietician can create a food plan Vitamin B12
that contains the right amount of Babies and children with MMA+HCU
protein, nutrients, and energy to keep may be given vitamin B12 injections in
your child healthy. Your child will need the form of hydroxocobalamin (OH-
to be on a special food plan throughout cbl). This treatment seems to lessen the
life. symptoms in some children but not
others. Your doctor may need to treat
Medical formula and foods
your child with OH-cbl for a short
In addition to a low-protein diet, your
period of time to determine whether
child may be given a special formula.
this treatment is useful.
This formula contains the correct
amount of protein and nutrients needed L-Carnitine
for normal growth and development. Some children with MMA+HCU may
Your metabolic doctor and dietician benefit by taking L-carnitine. This is a
will tell you whether your child needs safe and natural substance that helps
formula, what type is best, and how the body make energy. It also helps get
much to use. rid of harmful wastes. Your doctor will
decide whether or not your child needs
There are also medical foods such as
L-carnitine. Unless you are advised
special low-protein flours, pastas, and
otherwise, use only L-carnitine
rice that are made especially for people
prescribed by your doctor.
with organic acid disorders. Your
dietician will tell you how to use these Betaine
foods as part of your childs diet. Betaine is a vitamin-like substance
found in grains and other foods. It can
Some states offer help with payment or
also be bought in pill form as a
require private insurance to pay for the
supplement. Betaine helps lower the

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amount of homocysteine in the blood. It this. It is important that infants be fed


may lessen the risk of blood clots. Your during the night. They may need to be
metabolic specialist will decide woken up to eat if they do not wake up
whether your child needs betaine. He on their own. Your metabolic doctor
or she will need to write a prescription. and dietician will give you an
appropriate feeding plan for your
Hospital care
infant. Your doctor will also give you a
Children with extreme sleepiness or
sick day plan, tailored to your childs
lack of energy and those who are ill
needs, for you to follow during
may need to be treated in the hospital.
illnesses or other times when your
If your child has metabolic acidosis, he
child will not eat.
or she may be given medications such
as bicarbonate by IV to help reduce the Your metabolic doctor will continue to
acid levels in the blood. Glucose is advise you on how often your child
given by IV to prevent the breakdown should eat as he or she gets older.
of body stores of protein and fat.
4. Regular blood and urine tests
Do not use any medication without Your child will likely need regular
checking with your doctor or metabolic blood and urine tests to measure the
specialist. level of amino acids and other
substances. Your childs diet and
3. Avoid going a long time
medication may need to be adjusted
without food
based on the results of these tests.
Infants and young children with
MMA+HCU need to eat frequently to 5. Call your doctor at the start of
prevent a metabolic crisis. Your any illness
metabolic doctor will tell you how often In children with MMA+HCU, even
your child needs to be fed. In general, minor illness could lead to serious
it is often suggested that infants be fed health problems. In order to prevent
every four to six hours. Some babies problems, call your doctor right away
need to eat even more frequently than

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when your child has any of the Treatment may help some children but
following: not others. Even with treatment, some
loss of appetite babies and children may die. Others
vomiting may have life-long learning problems
diarrhea or mental retardation. Some children
infection or illness develop psychiatric disorders that are
fever difficult to treat.

When ill, your child needs extra fluids What causes the enzyme to be absent
and carbohydrates to prevent more or not working correctly?
serious health problems. During an Genes tell the body to make various
illness, you should restrict protein and enzymes. People with MMA+HCU have
give your child starchy foods and a pair of genes that do not work
fluids. correctly. Because of these gene
changes, the needed enzyme does not
Children with MMA+HCU may need to
work properly or is not made at all.
be treated in the hospital during
illness. Ask your metabolic doctor if How is MMA+HCU inherited?
you should carry a special travel letter
MMA+HCU is inherited in an
with medical instructions for your
autosomal recessive manner. It affects
childs care.
both boys and girls equally.
What happens when MMA+HCU is
treated?

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for MMA+HCU. They are called


carriers. Carriers do not have
MMA+HCU because the other gene of
this pair is working correctly.

When both parents are carriers, there


is a 25% chance in each pregnancy for
the child to have MMA+HCU. There is
a 50% chance for the child to be a
carrier, just like the parents. And, there
is a 25% chance for the child to have
two working genes.

Genetic counseling is available to


families who have children with
MMA+HCU. Genetic counselors can
answer your questions about how
MMA+HCU is inherited, choices during
future pregnancies, and how to test
other family members. Ask your doctor
about a referral to a genetic counselor.
Everyone has a pair of genes that make
the needed enzyme. In children with Is genetic testing available?

MMA+HCU, neither of these genes Genetic testing for MMA+HCU is

works correctly. These children inherit available. Genetic testing, also called

one non-working gene for the condition DNA testing, looks for changes in the

from each parent. pair of genes that cause MMA+HCU.


Talk with your genetic counselor or
Parents of children with MMA+HCU metabolic doctor if you have questions
rarely have the disorder. Instead, each about DNA testing.
parent has a single non-working gene

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DNA testing is not necessary to counselor can talk to you about your
diagnose your child. However, if choices and answer questions about
available, it can be helpful for carrier prenatal testing or testing your baby
testing or prenatal diagnosis, after birth.
discussed below.
Can other members of the family
What other testing is available? have MMA+HCU or be carriers?
Special tests on blood, urine, or skin
Having MMA+HCU
samples can be done to help confirm
If they are healthy and growing
MMA+HCU. Talk to your metabolic
normally, older brothers and sisters of
doctor or genetic counselor if you have
a baby with MMA+HCU are unlikely to
questions about testing for
have the condition. However, finding
MMA+HCU.
out if other children in the family have
Can you test during pregnancy? this condition may be important
If both gene changes have been found because early treatment may prevent
in your child with MMA+HCU, DNA serious health problems. Ask your
testing can be done during future metabolic doctor whether your other
pregnancies. The sample needed for children should be tested.
this test is obtained by either CVS or
MMA+HCU carriers
amniocentesis.
Brothers and sister who do not have
If DNA testing would not be helpful, MMA+HCU still have a chance to be
MMA+HCU can be detected by an carriers like their parents. Except in
enzyme test using cells from the fetus. special cases, carrier testing should
The sample needed for this test is only be done on people over 18 years.
obtained by CVS or amniocentesis.
Each of the parents brothers and
Parents may either choose to having sisters has a 50% chance to be a
testing during pregnancy or wait until carrier. It is important for other family
birth to have the baby tested. A genetic members to be told that they could be

291 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY

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carriers. There is a small chance they Where can Confirmatory Testing be


are also at risk to have children with done for this condition?
MMA+HCU. The confirmatory testing for the
disorder is done after B12
All states offer newborn screening for
supplementation and serial urine
MMA+HCU. However, when both
MMA and Homocysteine estimation by
parents are MMA+HCU carriers,
GC/MS.
newborn screening results are not
sufficient to rule out the condition in a Center

newborn baby. In this case, special PreventiNe Lifecare Pvt. Ltd.

diagnostic testing should be done in RPT House, Plot No. 6, Sector 24,

addition to newborn screening. Turbhe, Navi Mumbai 400705


Ph: 022-61980000/11
Can other family members be tested?
Diagnostic testing How many people have MMA+HCU
Brothers and sisters of a child with with homocystinuria?
MMA+HCU can have special tests on This condition is thought to be very
blood, urine, or skin samples. Talk to rare. The actual incidence is unknown.
your doctor or genetic counselor if you
Does MMA+HCU happen more
have questions about whether your
frequently in a certain ethnic group?
other children should be tested for
MMA+HCU does not occur more often
MMA+HCU.
in any specific race, ethnic group,
Carrier testing geographical area, or country.
If the gene changes have been
Does MMA+HCU with
identified in your child with
homocystinuria go by any other
MMA+HCU, carrier testing can be done
names?
for other family members. If you have
MMA+HCU is also sometimes called:
questions about carrier testing, ask
your genetic counselor or metabolic
doctor.

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Combined deficiency of
methylmalonyl CoA mutase and
homocystinuria
Methyltetrahydrofolate
methyltransferase deficiency
Vitamin B12 metabolic defect,
Type 2
Methylmalonic acidemia and
homocystinuria
Cbl C deficiency
Cbl D deficiency
Cbl F deficiency

Where can I find more information?


Organic Acidemia Association
http://www.oaanews.org

CLIMB (Children Living with Inherited


Metabolic Disorders)
http://www.climb.org.uk

Save Babies Through Screening


Foundation
http://www.savebabies.org/

Genetic Alliance
http://www.geneticalliance.org/

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P
Where can Confirmatory Testing
ropionic

be done for this condition?


Acidemia What is the cost of the
confirmatory test?
Disorder name: Propionic How many people have PA?
Acidemia Does PA happen more often in a
Acronym: PA certain ethnic group?
Does PA go by any other names?
What is PA?
Where can I find more
What causes PA?
information?
If PA is not treated, what
problems occur? This fact sheet contains general
What is the treatment for PA? information about PA. Every child is
What happens when PA is different and some of these facts may
treated? not apply to your child specifically.
What causes the PCC enzyme to Certain treatments may be
be absent or not working recommended for some children but
correctly? not others. All children with PA should
How is PA inherited? be followed by a metabolic doctor in
Is genetic testing available? addition to their primary care provider.
What other testing is available?
What is PA?
Can you test during pregnancy?
Can other members of the family
PA stands for propionic acidemia. It
have PA or be carriers?
is one type of organic acid disorder.
Can other family members be
People with PA have problems
tested?
breaking down and using certain
amino acids from the food they eat.

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What causes PA?


In order for the body to use protein
from the food we eat, it is broken down
into smaller parts called amino acids.

Organic Acid Disorders:


Organic acid disorders (OAs) are a
group of rare inherited conditions.
They are caused by enzymes that do
not work properly. A number of
enzymes are needed to process
protein from the food we eat for use by
the body. Problems with one or more
of these enzymes can cause an
organic acid disorder.

People with organic acid disorders


cannot break down protein properly. Special enzymes then make changes to
This causes harmful substances to the amino acids so the body can use
build up in their blood and urine. them.
These substances can affect health,
PA occurs when an enzyme called
growth and learning.
propionyl CoA carboxylase (PCC) is
The symptoms and treatment vary either missing or not working properly.
between different organic acid This enzymes job is to change certain
disorders. They can also vary from amino acids so the body can use them.
person to person with the same When this enzyme is not working,
organic acid disorder. See the fact substances called glycine and
sheets for each specific organic acid propionic acid, along with other
disorder.

Organic acid disorders are inherited


295 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY
in an autosomal recessive manner
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and affect both males and females.
BABYSHIELD TMS FACT SHEET

harmful substances, build up in the extreme sleepiness or lack of


blood and cause problems. energy
low muscle tone (floppy muscles
The four amino acids that cannot be
and joints)
used correctly are isoleucine, valine,
methionine, and threonine. These Common lab findings are:
amino acids are found in all foods that ketones in the urine
contain protein. Large amounts are high levels of acidic substances
found in meat, eggs, milk and other in the blood, called metabolic
dairy products. Smaller amounts are acidosis
found in flour, cereal, and some high blood ammonia levels
vegetables and fruits. high blood levels of glycine
high levels of certain organic
If PA is not treated, what problems
acids
occur?
low platelets
Each child with PA is likely to have
low white blood cells
somewhat different effects. Many
babies with PA start having symptoms If a metabolic crisis is not treated, a
in the first few days of life. Others have child with PA can develop:
their first symptoms sometime in breathing problems
infancy. There are also some people seizures
who have mild or no symptoms. swelling of the brain
stroke
PA causes episodes of illness called
coma, sometimes leading to
metabolic crises. Some of the first
death
symptoms of a metabolic crisis are:
A metabolic crisis can be triggered by:
poor appetite
eating large amounts of protein
vomiting
illness or infection
irritable mood
going too long without food
stressful events such as surgery

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Between episodes of metabolic crisis, What is the treatment for PA?


children with PA are often healthy. Your babys primary doctor will work
with a metabolic doctor and a dietician
Long-term effects are seen in some
to provide care for your child.
children with PA. These can include:
learning disabilities or mental Prompt treatment is needed to prevent
retardation mental retardation and serious medical
delays in walking and motor problems. Most children need to be on
skills a low-protein diet and drink a special
abnormal involuntary medical formula. You should start the
movements (dystonia or diet and formula as soon as you know
choreoathetosis) your child has PA.
rigid muscle tone, called
The following are treatments often
spasticity
recommended for children with PA:
poor growth with short stature
seizures 1. Low-protein diet, medical foods
osteoporosis and medical formula
inflammation of the pancreas,
Low-protein diet
called pancreatitis
A food plan low in the amino acids
vision loss due to problems with leucine, valine, methionine, and
the nerves in the eye threonine, with limited amounts protein
is often recommended. Most food in the
Without treatment, brain damage can
diet will be carbohydrates (bread,
occur. This can result in mental
cereal, pasta, fruit, vegetables, etc.).
retardation. If not treated, many babies
Carbohydrates give the body many
with PA die within the first year of life.
types of sugar that can be used as
A small number of people with PA energy. Eating a diet high in
never show symptoms and are only carbohydrates and low in protein can
found to be affected after a brother or help prevent metabolic crises.
sister is diagnosed.

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Foods high in protein that may need to and dietician will tell you what type of
be avoided or limited include: formula is best and how much to use.
milk and dairy products
There are also medical foods such as
meat and poultry
special low protein flours, pastas, and
fish
rice that are made especially for people
eggs
with organic acid disorders. Your
dried beans and legumes
dietician will tell you how to use these
nuts and peanut butter
foods as part of your childs diet. Some
Many vegetables and fruits have only states offer help with payment, or
small amounts of protein and can be require private insurance to pay for the
eaten in carefully measured amounts. formula and other special medical
Do not remove all protein from the diet. foods.
Children with PA need a certain
2. Avoid going a long time
amount of protein to grow properly.
without food
Your dietician will create a food plan Infants and young children with PA
that contains the right amount of need to eat frequently to prevent a
protein, nutrients, and energy to keep metabolic crisis. Your metabolic doctor
your child healthy. Your child will need will tell you how often your child needs
to be on a special food plan throughout to be fed. In general, it is often
his or her life. suggested that infants be fed every four
to six hours. Some babies need to eat
Medical formula and foods
even more frequently than this. It is
In addition to a low-protein diet, your
important that infants be fed during the
child may be given a special medical
night. They may need to be woken up
formula. This formula contains the
to eat if they do not wake up on their
correct amount of protein and nutrients
own. Your metabolic doctor and
needed for normal growth and
dietician will give you an appropriate
development. Your metabolic doctor
feeding plan for your infant. Your

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doctor will also give you a sick day proven to help in PA. But, your doctor
plan, tailored to your childs needs, for may talk with you about trying this
you to follow during illnesses or other supplement to see if it is of benefit to
times when your child will not eat. your child.

Your metabolic doctor will continue to Children who are having symptoms of
advise you on how often your child a metabolic crisis should be treated in
should eat as he or she gets older. the hospital. During a metabolic crisis,
your child may be given medications
3. Medication
such as bicarbonate by IV to help
Children with PA may benefit by taking
reduce the acid levels in the blood.
L-carnitine. This is a safe and natural
Glucose is often given by IV to prevent
substance that helps the body make
the breakdown of protein and fat stored
energy. It also helps get rid of harmful
in the body.
wastes. L-carnitine is part of the usual
treatment for PA. Your doctor will tell Do not use any medication or
you how much your child needs. supplement without first checking with
Unless you are advised otherwise, use your doctor or metabolic doctor.
only L-carnitine prescribed by your
4. Regular blood and urine tests
doctor.
Tracking of ketones
Certain antibiotics, taken by mouth, Your child will have periodic urine
can help reduce the amount of tests to check the level of ketones.
propionic acid in the intestines. Your These can be done at home or at the
doctor will decide if your child needs doctors office. Ketones are substances
antibiotics and, if so, what type. formed when body fat is broken down
for energy. This can happen after going
Some children may be given biotin
without food for long periods of time,
supplements by mouth. Biotin is a type
as the result of an illness, or during
of B vitamin that helps the body make
periods of heavy exercise. Ketones in
energy from food. Biotin has not been

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the urine may signal the start of a metabolic crisis. In addition, they
metabolic crisis. should avoid eating protein during any
illness.

Many children with PA need to be


Blood tests treated in the hospital during illness to
Your child will have regular blood tests avoid serious health problems. Ask
to measure the levels of amino acids. your metabolic doctor if you should
Urine tests may also be done. Your carry a special travel letter with
childs diet and medication may need to medical instructions for your childs
be adjusted based on the results of care.
these tests.
5. Liver transplant
4. Call your doctor at the start of Liver transplant surgery is an optional
any illness treatment for people with PA. The PCC
In children with PA, even minor illness enzyme that causes PA is located in the
can lead to a metabolic crisis. In order liver. Because of this, some children
to prevent problems, call your doctor with PA have had liver transplantation
right away when your child has any of surgery (removal of their liver and
the following: replacement with a donor liver) to treat
their PA symptoms.
loss of appetite
vomiting This major surgical procedure is
diarrhea associated with risks, and individuals
infection or illness who have had a liver transplant must
fever take medication for the rest of their
lives to prevent their body from
Children with PA need to eat more
rejecting the donor liver. However,
starchy foods and drink more fluids
even with a successful liver
when they are ill even if they arent
transplantation people with PA may
hungry or they could have a
still need to have a restricted diet.

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Many factors must be considered How is PA inherited?


before surgery and this option should PA is inherited in an autosomal
be discussed very thoroughly with your recessive manner. It affects both boys
childs physicians. and girls equally.

What happens when PA is treated? Everyone has a pair of genes that make
Babies who have prompt and ongoing the PCC enzyme. In children with PA,
treatment before they have a metabolic neither of these genes works correctly.
crisis may have normal growth and These children inherit one non-working
development. In general, the earlier gene for the condition from each
treatment is started, the better the parent.
outcome.
Parents of children with PA rarely have
Even with treatment, some children the disorder themselves. Instead, each
have life-long learning problems or parent has a single non-working gene
mental retardation. Seizures or for PA. They are called carriers.
problems with involuntary movements Carriers do not have PA because the
also occur in some children, despite other gene of this pair is working
treatment. Children with PA often have correctly.
more infections than usual. These need
When both parents are carriers, there
to be treated promptly to avoid a
is a 25% chance in each pregnancy for
metabolic crisis.
the child to have PA. There is a 50%
What causes the PCC enzyme to be chance for the child to be a carrier, just
absent or not working correctly? like the parents. And, there is a 25%
Genes tell the body to make various chance for the child to have two
enzymes. People with PA have a pair of working genes.
genes that do not work correctly.
Because of these gene changes, the
PCC enzyme does not work properly or
is not made at all.

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Talk with your genetic counselor or


metabolic doctor if you have questions
about DNA testing.

DNA testing is not necessary to


diagnose your child. However, it can be
helpful for carrier testing or prenatal
diagnosis, discussed below.

What other testing is available?


Special tests on blood, urine or skin
samples can be done to confirm PA.
Talk to your metabolic doctor or
genetic counselor if you have questions
about testing for PA.

Can you test during pregnancy?


Genetic counseling is available to
If both gene changes have been found
families who have children with PA.
in your child with PA, DNA testing can
Genetic counselors can answer your
be done during future pregnancies. The
questions about how PA is inherited,
sample needed for this test is obtained
choices during future pregnancies, and
by either CVS or amniocentesis.
how to test other family members. Ask
your doctor about a referral to a genetic PA can also be found through an
counselor. enzyme test using cells from the fetus.
The sample needed for this test is
Is genetic testing available?
obtained by amniocentesis.
Genetic testing for PA can be done on a
blood sample. Genetic testing, also Parents may either choose to have
called DNA testing, looks for changes testing during pregnancy or wait until
in the pair of genes that causes PA. birth to have the baby tested. A genetic

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counselor can talk to you about your are also at risk to have children with
choices and answer questions about PA.
prenatal testing or testing your baby
All states offer newborn screening for
after birth.
PA. However, when both parents are
Can other members of the family PA carriers, newborn screening results
have PA or be carriers? are not sufficient to rule out the
condition in a newborn baby. In this
Having PA
case, special diagnostic testing should
Older brothers and sisters of a baby
be done in addition to newborn
with PA, if they are healthy and
screening.
growing normally, are unlikely to have
the condition. However, finding out if Can other family members be tested?
other children in the family have this
Diagnostic testing
condition may be important because
Brothers and sisters of a child with PA
treatment can prevent serious health
can have special tests on blood, urine
problems. Ask your metabolic doctor or
or skin samples. Talk to your doctor or
genetic counselor whether your other
genetic counselor if you have questions
children should be tested.
about testing for PA.
PA carriers
Carrier testing
Brothers and sister who do not have
Carrier testing for PA may be available.
PA still have a chance to be carriers
If you have questions about carrier
like their parents. Except in special
testing, ask your genetic counselor or
cases, carrier testing should only be
metabolic doctor.
done on people over 18 years of age.
Each of the parents brothers and
Where can Confirmatory Testing be
sisters has a 50% chance to be a PA
done for this condition?
carrier. It is important for other family
members to be told that they could be The confirmatory test for the
carriers. There is a small chance they diagnosis is done by Gas

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Chromatography Mass Spectrometry Does PA happen more frequently in a


(GC/MS) using urine sample or by certain ethnic group?
estimation of Propionyl CoA PA occurs in all ethnic groups around
carboxylase enzyme activity measured the world. It is found more often in the
in cultured fibroblast cells from Arab population of Saudi Arabia and
patient. the Inuit population of Greenland.
About one in 2000 to one in 5000
Center
babies of Saudi Arabian ancestry is
PreventiNe Lifecare Pvt. Ltd.
born with PA. And, about one in 1000
RPT House, Plot No. 6, Sector 24,
babies in the Inuit population of
Turbhe, Navi Mumbai 400705
Greenland has PA.
Ph: 022-61980000/11
Does PA go by any other names?
Academic Medical Center
PA is sometimes also called:
Laboratory Genetic Metabolic Diseases
Propionyl-CoA carboxylase
(F0-132)
deficiency
Meibergdreef 9
PCC deficiency
1105 AZ Amsterdam
Ketotic glycinemia
The Netherlands
Ketotic hyperglycinemia
Ph: +31 20 5662026 / 5393
E-mail: gmz_enzym@amc.nl Where can I find more information?
Propionic Acidemia Foundation
What is the cost of the confirmatory
http://www.pafoundation.com
test?
680 (+ 150 for fibroblast culturing
Propionic Acidemia Research Network
from skin biopsy)
http://www.paresearch.org/

How many people have PA? Organic Acidemia Association


About 1 in every 100,000 babies in the
http://www.oaanews.org
United States is born with PA.

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CLIMB (Children Living with Inherited


Metabolic Disorders)
http://www.climb.org.uk

Save Babies Through Screening


Foundation
http://www.savebabies.org/

Genetic Alliance
http://www.geneticalliance.org/

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3 -Methylcrotonyl
CoA Carboxylase


Where can Confirmatory Testing
be done for this condition?
What is the cost of the
Deficiency confirmatory test?
Disorder name: 3-methylcrotonyl How many people have 3MCC
CoA carboxylase deficiency deficiency?
Acronym: 3MCC deficiency Does 3MCC deficiency happen
more often in a certain ethnic
What is 3MCC deficiency?
group?
What causes 3MCC deficiency?
Does 3MCC deficiency go by any
If 3MCC deficiency is not treated,
other names?
what problems occur?
Where can I find more
What is the treatment for 3MCC
information?
deficiency?
What happens when 3MCC This fact sheet has general information
deficiency is treated? about 3MCC deficiency. Every child is
What causes the 3MCC enzyme to different and some of these facts may
be absent or not working not apply to your child specifically.
correctly? Certain treatments may be
How is 3MCC deficiency recommended for some children but
inherited? not others. Children with 3MCC
Is genetic testing available? deficiency should be followed by a
What other testing is available? metabolic doctor in addition to their
Can you test during pregnancy? primary doctor.
Can other members of the family
What is 3MCC deficiency?
have 3MCC deficiency or be
3MCC deficiency is one type of organic
carriers?
acid disorder. Some children with this
Can other family members be
condition have problems breaking
tested?

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down an amino acid called leucine


from the food they eat.

What causes 3MCC deficiency?

Organic Acid Disorders:


Organic acid disorders (OAs) are a
group of rare inherited conditions.
They are caused by enzymes that do
not work properly. A number of
enzymes are needed to process
protein from the food we eat for use by
the body. Problems with one or more
of these enzymes can cause an
organic acid disorder.

People with organic acid disorders


cannot break down protein properly.
This causes harmful substances to In order for the body to use protein
build up in their blood and urine. from the food we eat, it is broken down
These substances can affect health, into smaller parts called amino acids.
growth and learning. Special enzymes then make changes to
the amino acids so the body can use
The symptoms and treatment vary
them.
between different organic acid
disorders. They can also vary from 3MCC deficiency occurs when an
person to person with the same enzyme, called 3-methylcrotonyl CoA
organic acid disorder. See the fact carboxylase (3MCC), is either missing
sheets for each specific organic acid or not working properly. This enzymes
disorder. job is to help break down leucine.

Organic acid disorders are inherited


307 NEWBORN SCREENING- SCREEN EARLY TREAT EARLY
in an autosomal recessive manner
Unauthorised reproduction of this article is prohibited
and affect both males and females.
BABYSHIELD TMS FACT SHEET

When a child with 3MCC deficiency irritable mood


eats food containing leucine, harmful muscle weakness
substances may build up in the blood nausea
and cause problems. Leucine is found vomiting
in all foods with protein.
Common blood and urine findings are:
If 3MCC deficiency is not treated, low blood sugar, called
what problems occur? hypoglycemia
Each child with 3MCC deficiency may increased levels of acidic
have somewhat different effects. In substances in the blood, called
fact, some children with this condition metabolic acidosis
never have symptoms and may not high levels of ammonia in the
ever need treatment. blood
low levels of carnitine in the
Babies with 3MCC deficiency are
blood
healthy at birth. If symptoms occur,
increased ketones in the urine
they often start after 3 months of age.
liver problems
Some babies do not have their first
symptoms until 6 months to 3 years of If a metabolic crisis is not treated, a
age. Others do not have symptoms child with 3MCC deficiency can
until adulthood. Some people will never develop:
develop symptoms. breathing problems
seizures
3MCC deficiency can cause episodes of
liver failure
illness called metabolic crises. Some of
coma, sometimes leading to
the first symptoms of a metabolic crisis
death
are:
poor appetite If a metabolic crisis is not treated, it
extreme sleepiness or lack of could result in death. In surviving
energy babies and children, repeated episodes
behavior changes of metabolic crisis can cause brain

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damage. This can lead to life-long Some people do not have any
learning problems or mental symptoms until adulthood. Some of the
retardation. symptoms seen in adults are:
weakness
Episodes of metabolic crisis can be
fatigue
triggered by:
Some people with 3MCC deficiency
illness or infection
never have symptoms and are only
going without food for long
found to be affected after a brother or
periods of time
sister is diagnosed, or they may be
eating large amounts of protein
diagnosed through newborn screening.

When a child is ill or goes without food


What is the treatment for 3MCC
for too long, the body breaks down its
deficiency?
own protein and fat to use for energy.
Your babys primary doctor may work
In some people with 3MCC deficiency,
with a metabolic doctor and a dietician
this can trigger a metabolic crisis.
to care for your child.

Between episodes of metabolic crisis,


In some children, prompt treatment is
children with 3MCC deficiency are
needed to prevent metabolic crises and
usually healthy.
the health effects that follow. Certain
treatments may be advised for some
Some children do not ever have
children but not others. Children who
metabolic crises. However, they may
do not show symptoms may not need
have other symptoms. These can
treatment.
include:
poor growth and development
The following are treatments that are
either low muscle tone or
used for some babies and children with
spasticity
3MCC deficiency:

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1. Low-leucine diet, including If needed, your dietician will create a


medical foods and formula food plan that contains the right
A food plan low in leucine with limited amount of protein, nutrients and
amounts of protein is sometimes energy for your child. Some children
needed. Most food in the diet will be may be on a special food plan
carbohydrates (bread, cereal, pasta, throughout life.
fruit, vegetables, etc.). Carbohydrates
give the body many types of sugar that Medical foods and formula
can be used as energy. Eating a diet There are medical foods such as
high in carbohydrates and low in special low-protein flours, pastas, and
protein can help prevent hypoglycemia rice that are made especially for people
and metabolic crises. with organic acid disorders. If
necessary for your child, your dietician
Foods high in protein that may need to
will tell you how to use these foods.
be avoided or limited include:
milk and dairy products In addition to a low-protein diet, some
meat and poultry children are given a special leucine-free
fish medical formula. Your metabolic doctor
eggs and dietician will decide whether your
dried beans and legumes child needs this formula. Some states
nuts and peanut butter offer help with payment, or require
private insurance to pay for the formula
Many vegetables and fruits have only
and other special medical foods.
small amounts of protein and can be
eaten in carefully measured amounts. 2. Medications
Do not remove all protein from the diet. Some children may benefit by taking L-
Children with 3MCC deficiency need carnitine. This is a safe and natural
small amounts of protein to grow substance that helps body cells make
properly. energy. It also helps the body get rid of
harmful wastes. Your doctor will

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decide whether or not your child needs metabolic crisis. They should also
L-carnitine. Unless you are advised avoid eating protein during any illness.
otherwise, use only L-carnitine
Children who are ill often dont want to
prescribed by your doctor.
eat. If they cant eat, or if they show
Your doctor may suggest other signs of a metabolic crisis, they may
medications or supplements that may need to be treated in the hospital. Ask
be helpful in preventing some of the your metabolic doctor if you should
symptoms of 3MCC deficiency. Do not carry a special travel letter with
use any medication without checking medical instructions for your childs
with your doctor. care.

3. Call your doctor at the start of any What happens when 3MCC
illness deficiency is treated?
In some children, even minor illnesses Many children found to have 3MCC
such as a cold or the flu can lead to a during newborn screening will never
metabolic crisis. In order to prevent need treatment.
problems, you may be told to call your
With prompt and careful treatment,
doctor right away when your child has
children who have shown symptoms of
any of the following:
3MCC deficiency have a good chance
loss of appetite
to live healthy lives with typical growth
vomiting
and development.
diarrhea
infection or illness
Even with treatment, some children
fever still have repeated bouts of metabolic
crisis. This can cause brain damage
Some children need to eat more
and may lead to life-long learning
carbohydrates and drink more fluids
problems or mental retardation.
when they are ill even if theyre not
hungry or they could have a

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What causes the 3MCC enzyme to be When both parents are carriers, there
absent or not working correctly? is a 25% chance in each pregnancy for
Genes tell the body to make various the child to have 3MCC deficiency.
enzymes. People with 3MCC deficiency There is a 50% chance for the child to
have a pair of genes that do not work be a carrier, just like the parents. And,
correctly. Because of the changes in there is a 25% chance for the child to
this pair of genes, the 3MCC enzyme have two working genes.
either does not work properly or is not
made at all.

How is 3MCC deficiency inherited?


3MCC deficiency is inherited in an
autosomal recessive manner. It affects
both boys and girls equally.

Everyone has a pair of genes that make


the 3MCC enzyme. In children with
3MCC deficiency, neither of these
genes works correctly. These children
inherit one non-working gene for the
condition from each parent.

Parents of children with 3MCC


deficiency rarely have the disorder.
Instead, each parent has a single non-
working gene for 3MCC deficiency.
They are called carriers. Carriers do Genetic counseling is available to
not have the condition because the families who have children with 3MCC
other gene of this pair is working deficiency. Genetic counselors can
correctly. answer your questions about how the
condition is inherited, choices during

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future pregnancies, and how to test this test is obtained by either CVS or
other family members. Ask your doctor amniocentesis.
about a referral to a genetic counselor.
It may also be possible to test for
Is genetic testing available? 3MCC deficiency using an enzyme test
Genetic testing for 3MCC deficiency on cells from the fetus. The sample
can be done on a blood sample. needed for this test is obtained by
Genetic testing, also called DNA either CVS or amniocentesis.
testing, looks for changes in the pair of
Parents may choose to have testing
genes that causes 3MCC deficiency.
during pregnancy or wait until birth to
Talk with your genetic counselor or
have the baby tested. A genetic
metabolic doctor if you have questions
counselor can talk to you about your
about DNA testing.
choices and answer questions about
DNA testing is not necessary to prenatal testing or testing your baby
diagnose your child. However, it can be after birth.
helpful for carrier testing or prenatal
Can other members of the family
diagnosis, discussed below.
have 3MCC deficiency or be carriers?
What other testing is available?
Having 3MCC deficiency
Special tests on blood, urine or skin
The brothers and sisters of a baby with
samples can be done to confirm 3MCC
3MCC deficiency have a chance of
deficiency. Talk to your metabolic
being affected even if they havent had
doctor if you have questions about
symptoms. Finding out whether other
testing for this condition.
children in the family have this
Can you test during pregnancy? condition may be important because
If both gene changes have been found early treatment may prevent serious
in the child with 3MCC deficiency, health problems. Ask your metabolic
DNA testing can be done during future doctor whether your other children
pregnancies. The sample needed for should be tested.

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3MCC deficiency carriers Can other family members be tested?


Brothers and sisters who do not have
Diagnostic testing
3MCC deficiency still have a chance to
Brothers and sisters of a child with
be carriers like their parents. Except in
3MCC deficiency can be tested using
special cases, carrier testing should
blood, urine, or skin samples.
only be done in people over 18 years of
age. Carrier testing
If both gene changes have been found
Each of the parents brothers and
in your child with 3MCC deficiency,
sisters has a 50% chance to be a
other family members can have DNA
carrier. It is important for other family
testing to see if they are carriers.
members to be told that they could be
carriers. There is a small chance they
If DNA testing is not possible or is not
are also at risk to have children with
helpful, other methods of carrier testing
3MCC deficiency. may be available. Your metabolic
doctor or genetic counselor can answer
Almost all states offer newborn
your questions about carrier testing.
screening for 3MCC deficiency.
However, expanded newborn screening
through private labs is available for
babies born in states that do not screen Where can Confirmatory Testing be
for this condition. done for this condition?
The confirmatory test for the
When both parents are carriers for
diagnosis is done by estimation of 3-
3MCC deficiency, newborn screening Methyl-crotonyl-CoA carboxylase
results are not sufficient to rule out the
activity in the cultured skin
condition in a newborn baby. In this
fibroblasts.
case, special diagnostic testing should
be done in addition to newborn Center

screening. Academic Medical Center


Laboratory Genetic Metabolic Diseases

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(F0-132) The adult form of 3MCC deficiency is


Meibergdreef 9 also called:
1105 AZ Amsterdam
Late-onset 3-methylcrotonyl CoA
the Netherlands
carboxylase deficiency
Ph: +31 20 5662026 / 5393
E-mail: gmz_enzym@amc.nl Where can I find more information?

What is the cost of the confirmatory Organic Acidemia Association


test?
http://www.oaanews.org
350 (+ 100 for fibroblast culturing)
Save Babies Through Screening
How many people have 3MCC Foundation
deficiency?
http://www.savebabies.org/
About one in every 50,000 babies in the
United States is born with 3MCC CLIMB (Children Living with Inherited
deficiency. Metabolic Disorders)
http://www.climb.org.uk
Does 3MCC deficiency happen more
frequently in a certain ethnic group? Genetic Alliance
No, this condition does not happen http://www.geneticalliance.org/
more often in any specific race, ethnic
group, geographical area or country.

Does 3MCC deficiency go by any


other names?
3MCC deficiency is sometimes also
called:

3-methylcrotonylglycinuria
Methylcrotonyl-CoA carboxylase
deficiency

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2
BABYSHIELD TMS FACT SHEET

Where can Confirmatory Testing


-Methylbutyryl

be done for this condition?


CoA
What is the cost of the
Dehydrogenase confirmatory test?
Deficiency How many people have 2MBCD

Disorder name: 2-methylbutyryl CoA deficiency?


dehydrogenase deficiency Does 2MBCD deficiency happen
Acronym: 2MBCD deficiency more often in a certain ethnic
group?
What is 2MBCD deficiency? Does 2MBCD deficiency go by any
What causes 2MBCD deficiency? other names?
If 2MBCD deficiency is not Where can I find more
treated, what problems occur? information?
What is the treatment for 2MBCD
deficiency? This fact sheet has general information
What happens when 2MBCD about 2MBCD deficiency. Every child
deficiency is treated? is different and some of these facts may
What causes the 2MBCD enzyme not apply to your child specifically.

to be absent or not working Certain treatments may be

correctly? recommended for some children but


How is 2MBCD deficiency not others. Children with symptoms of
inherited? 2MBCD deficiency should be followed
Is genetic testing available? by a metabolic doctor in addition to

What other testing is available? their primary doctor.

Can you test during pregnancy?


What is 2MBCD deficiency?
Can other members of the family
have 2MBCD deficiency or be 2MBCD deficiency is one type of
carriers? organic acid disorder. Some children
Can other family members be with 2MBCD deficiency have problems
tested?

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breaking down an amino acid called


person to person with the same
isoleucine from the food they eat.
organic acid disorder. See the fact
sheets for each specific organic acid
disorder.

Organic acid disorders are inherited


in an autosomal recessive manner
and affect both males and females.
Organic Acid Disorders:
Organic acid disorders (OAs) are a What causes 2MBCD deficiency?
group of rare inherited conditions.
In order for the body