Metabolic Emergencies

and their Management

James B. Gibson, MD, PhD
Division of Genetics and Metabolic Disorders
Department of Pediatrics, UTHSCSA
Dr.Muhammed .A. Jabbar NRC
 Objectives
• Recognize common presentations of
metabolic disease requiring immediate
responses
• Know how to organize the first steps of the
evaluation for metabolic disease
• Be able to direct initial management of the
patient with suspected metabolic disease
• Know how to stabilize the patient with known
metabolic disease
 What are Metabolic Diseases
• Inborn errors of biochemistry
• Frequency of 1/200 or less
• Detection: screening or symptoms
• Genetics: recessive, X-linked,
mitochondrial, dominant
• May or may not be treatable
 Clinical Presentations
• Neurological alterations, seizures, coma
• Multiple organ system failure
• Acidosis
• Hyperammonemia
• SIDS/ALTE
• Failure to thrive
• Hepatic or renal dysfunction
• Malformations
• Organomegaly and
coarsening of features
• Hematologic abnormalities
• Orthopedic concerns
• Developmental delays or
regression
• Aggression
• Psychiatric symptoms
• Asymptomatic
 Time of Initial Presentation
• Neonatal (<28 days of age)
• Infancy (1 month to 1 year)
• Childhood (over 1 year)
• Adolescence
• Adulthood
 Differential Diagnosis in Sick
Neonate
• Sepsis
• Hypoglycemia
• Congenital Cardiac Disease
• Intracranial Bleed
• Electrolyte Imbalance (Ca2+, Mg2+, Na+, K+, …)
• Endocrine Disease
• Inborn Error of Metabolism
• Syndrome (Dysmorphic/ Chromosomal Dx)
• Toxin
 Metabolic Approach to Sick
Neonate
• Onset: Hours to Days
• Poor Feeding
• Vomiting
• Hypotonia / Hypertonia
• Tachypnea
• Lethargy -- Stupor-- Coma
• Unusual Odor (Urine, Breath, Skin, Cerumen)
• Seizures
• Apnea
 Approach to Sick Neonate
• Always consider the possibility of an
inborn error of metabolism
• Initial tests: Blood gas, Anion gap,
Glucose, Ketones, Ammonia, Lactate
• Stop protein feeds
• Give maximal calories from glucose
• Secondary tests: plasma Amino Acids,
Lactate/pyruvate, Carnitine, Urine Organic
Acids, Orotic Acid
Diagnostic Clues for Metabolic
Diseases
• History
– Family history
– Feeding history
– Past Medical history
– Developmental history
• Physical Examination
– Special clues in general examination
– Neurologic signs
 Dysmorphism in IEM
• Head and Face
– Forehead high or big
– Fontanel big anterior
– Hair pattern
– Eye
• wide spacing
• cataracts or corneal clouding
– Ear placement low
• Genitalia
– Hypospadius
– Ambiguous genitalia / virilized
 Other Malformations in IEM
• Brain
– Heterotopias
– Absence of corpus
callosum
• Kidney
– Multicystic dysplasia
• Heart
– Dilated cardiomyopathy
– Hypertrophic cardiomyopathy
• Abnormal fat pads
• Inverted nipples
 Laboratory Findings in IEMs
• Hypoglycemia
• Metabolic Acidosis
• Respiratory Alkalosis
• Ketosis
• Hyperammonemia
• Anemia, Leukopenia, Thrombocytopenia
• Urinary Reducing Substances
• Abnormal LFTs, Hyperbilirubinemia
• Inclusions in circulating WBCs
 Critically ill infant: coma, intractable seizures,
respiratory distress, cardiovascular collapse

Basic Lab tests: glucose, electrolytes

arterial blood gas, ammonia, urinalysis

hypoglycemia metabolic acidosis

Major Abnormality

hyperammonemia no abnormality
Major Abnormality
Fatty acid oxidation
hypoglycemia
Disorder of CHO metabolism

Critical samples Blood insulin, GH, cortisol

3OHB/AcAc, FFA, lactate
Urine organic acids, reducing
substances

hyperammonemia Urea cycle disorder

Blood amino acids

Critical samples Urine orotic acids
Major Abnormality
no abnormality Organic aciduria, NKH, Sulfite oxidase,
Pyridoxine responsive seizure,
Neurotransmitter disease
Critical samples Blood amino acids, lactate
Urine organic Acids
CSF lactate, neurotransmitters
**ketosis (DNPH) MSUD
Critical samples Blood amino acids
Urine organic Acids
metabolic acidosis Organic aciduria, lactic acidoses
Blood amino acids, lactate
Critical samples Urine organic Acids
CSF lactate
 Hyperammonemia
• Normal ranges
– Newborn 64 - 107 micromol/L
– Adult 13 - 34 micromol/L
• Acute hyperammonemia: progression of
combativeness to lethargy to coma to death
• Neonatal Presentation
– Lethargy, anorexia, vomiting, apnea, seizures, coma
• Acute, catastrophic; often fatal
• Infantile (subacute)
– FTT, developmental delay, seizures, ataxia, hepatomegaly,
cerebral atrophy
– Stress/fever/catabolism-induced episodic
 Sx Low pH Ketosis Lactate NH3 Glu Possible
Neuro 0 ++ 0 0 N MSUD
Neuro + ++ 0 + N Organic a

Neuro ++ + ++ 0 N,D Lactic acid

Neuro 0 0 0 ++ N Urea Cycl

Neuro 0 0 0 0 N NKH, ETC
Peroxisom

Liver + + + 0 D GSD
Liver + 0 0 0 D FAO Defe
Heart Modified from J-M Saudubray, 2001 MMBID
 Urea Cycle Disorders
• Encephalopathy (progressive), hyperpnea
• Hepatopathy and hyperammonemia
• No to minimal acidosis
• Glucose and CBC normal
• Lactate normal to increased
• Neonatal illness
– Hyperammonemia, coma, cerebral edema
• Illness in older patients
– Recurrent presentation like neonatal illness
– Vomiting, abnormal liver enzymes, episodic hepatomegaly
with ataxia, Reye syndrome, psychiatric illness
 Urea Cycle Enzyme Defects
Ammonium+ + bicarbonate + ATP
Carbamyl Phosphate

• Immediate work-up Synthase

CARBAMYL PHOSPHATE
Ornithine
– Plasma amino acids Transcarbamylase
ORNITHINE
– Urine orotic acid Arginase CITRULLINE
UREA
• Other evaluation ARGININE Aspartate
Fumaric
– Enzyme/DNA studies acid

Argininosuccinate Argininosuccinate
– Liver tissue Lyase ARGININOSUCCINIC Synthase
ACID

• Autosomal recessive
– Except ornithine transcarbamylase
deficiency (OTCD) which is X-linked
 Encephalopathy & Ketones
• Normal lactate and glucose,
• Ammonia normal to increased
• Keto-acids present (+ DNPH)
• Odor in urine or cerumen
• Alternating hyper- and hypotonia
• Cerebral edema, seizures
• Maple Syrup Urine Disease
– Branched chain ketoacid dehydrogenase
defect Sx Low pH Ketosis Lactate NH3 Glu Possibl
Neuro 0 ++ 0 0 N MSUD
• Plasma amino acids Neuro + ++ 0 + N Organic

Neuro ++ + ++ 0 N,D Lactic ac

– Urine organic acids Neuro 0 0 0 ++ N Urea Cy
Neuro 0 0 0 0 N NKH, ET
Peroxiso

Liver + + + 0 D GSD
 Encephalopathy, Acidosis
and Ketosis
• Increased anion gap
• NH3 may be moderately increased
• Lactate normal to increased
• Glucose may be normal to increased
• Calcium normal to decreased
• Leucopenia or Thromocytopenia
• Organic acidemias
– Or ketolytic defects
• Urine organic acids &
Sx Low pH Ketosis Lactate NH3 Glu Possible
Neuro 0 ++ 0 0 N MSUD
Neuro + ++ 0 + N Organic a

Carnitine, Acylcarnitine Neuro ++ + ++ 0 N,D Lactic acid

Profiles
Neuro 0 0 0 ++ N Urea Cycl
Neuro 0 0 0 0 N NKH, ETC
Peroxisom

Liver + + + 0 D GSD
Liver + 0 0 0 D FAO Defe
 Prototypical Organic Acidemias
• Propionic acidemia (carboxylase)
– Propionyl-Co A inhibits other systems
• PDH complex; N-acetyl-glutamate synthase; glycine
cleavage system
• Isovaleric acidemia (dehydrogenase)
• Methylmalonic Acidemia (mutase)
• Treatment
– Low amino acid diet and carnitine
– Glycine, thiamine, cobalamin or biotin in some
cases
– Hydration
– Metronidazole?
Diagnosis of Organic Acidemias
• Traditional
– Urinary Organic Acids by GC/MS
– Enzyme Analysis
• Dried Filter Paper Urine Sample
– Stable isotope dilution GC/MS
– Sample stable for two weeks
– Potential use in neonatal screening
• Proton NMR spectroscopy
– Use of underivitized material
• MS/MS from Dried Blood Spots
ODOR COMPOUND DISORDER
Maple syrup Isoleucine metabolitesM aple Syrup Urine Dise
sweet

Musty Phenylacetic acid Phenylketonuria (PKU)

Sweaty feet Isovalerate Isovaleric Acidemia

Cheesy Glutaric Aciduria, type II

Cabbage a-Ketomethylbutyrate Tyrosinemia, type I

Hypermethionemia

Tomcat’s Methylcrotonic acid Methylcrotonic Acidemia

Urine Multiple Carboxylase De

Fishy Trimethylamine Trimethylaminuria

 Metabolic Acidosis: Lactate
• Encephalopathy
• May have no normal period after birth
• Acetone normal to increased
• Anion gap increased
• Glucose and NH3 normal to decreased

• Pyruvate dysmetabolism, TCA cycle

and Respiratory chain defects
• Labs
– Lactate/pyruvate
– Quantitative ketones
– Urine organic acids
– Enzyme studies
 Alanine Protein
Carbohydrate Lactate AAT
LDH Leucine Valine
Glucose Pyruvate
Isoleucine
PDH
PC
PEP Krebs Acetyl CoA Propionate
Cycle
Oxaloacetate Ketones
Succinate Fatty Acids
ATP Fat
Urea cycle Methylmalonate
ETC NH4
 Intermembrane Space
H+

Cyto
e- CoQ C
I III IV V

II
NADH NAD ½ O2 H2O

Succinate Fumarate ADP + Pi ATP

Matrix H+
 Lab Tests
• Lactate and Pyruvate
– Cytoplasmic redox state
– Normal ratio: 10-20
• Low ratio, even if normal concentrations: PDH
• 3-Hydroxybutyrate/Acetoacetate (Ketone bodies)
– Mitochondrial redox state
• High L/P ratio >30; postprandial ketonemia
and normal ketone ratio(<1.5) PC/ α KGDD
• High L/P ratio >30 (and ketone ratio >2.0)
Respiratory Chain Defects
 Lactic Acidoses
• May need more than one set of labs
• Subset of disorders with lactate increased by
feeding
• GSD 1, PDH, PC, certain respiratory chain defects,
Multiple Carboxylase Defects, α −KGDD
• Other diseases show highest lactate after fasting

• GSD III/VI, Glycogen synthase, FAOD & Fructose

diphosphatase
• Permanent
– Neurologic signs or >10mM Congenital LA
– Hypoglycemia and Hepatomegaly GSD I
 Lab Testing for ETC Defects
• Blood (may need fasting and fed samples)
– Lactate, pyruvate, β -hydroxybutyrate,
acetoacetate, plasma amino acids
– ? Forearm ischemia or treadmill tests
• Urine: organic acids, amino acids
• CSF: lactate, pyruvate, ?neurotransmitters
• Fibroblasts and Muscle for enzymology
– can use other organs with controls
• DNA studies: blood, muscle, other organs
 Acidosis and Hypoglycemia
• Acetone, Ketones negative
• NH3 and lactate normal to increased
• Hepatic or cardiac symptoms
• Seizures with hypoglycemia
• Fatty acid oxidation defects
• Ketogenesis defects
– ? Respiratory chain defects
• Organic Acids &
Sx Low pH Ketosis Lactate NH3 Glu Possib

Carnitine, Acylcarnitine Neuro

Neuro
0
+
++
++
0
0
0
+
N
N
MSUD
Organic

Profiles Neuro

Neuro
++

0
+

0
++

0
0

++
N,D Lactic a

N Urea Cy
Neuro 0 0 0 0 N NKH, E
Peroxis

Liver + + + 0 D GSD
 C10-C24 (26) L-Carnitine C4-C8(9/10)
FABP
CT Plasma
Membrane

A CPT 1 OMM
S
CoASH L-Carnitine
LC acyl-CoA
LC acylcarnitine

TRANS IMM
L-Carnitine CPT 2 CoASH
AS

MC acyl-CoA
LC acylcarnitine
CoASH LC acyl-CoA
β -oxidation spiral
 FAD FADH

Acyl-CoA 2,3-Enoyl-CoA
(R-CH2-CH2-CO-SCoA) 1 (R-CH=CH-CO-SCoA)
CH=CH
H2O
Acetyl-CoA

4 5 HMG-CoA
6 7 2
Acetoacetyl-CoA Acetoacetate
CoASH
3-Hydroxybutyrate

3-Oxoacyl-CoA 3-hydroxyacyl-CoA
O 3 OH
II NADH NAD I
(R-C-CH2-CO-SCoA) (R-CH-CH2-CO-SCoA)
MCAD Signs and Symptoms
Symptom/sign Percent Affected
Lethargy 84
Emesis 66
Encephalopathy 49
Respiratory arrest 48
Hepatomegaly 44
Seizures 43
Apnea 37
Cardiac arrest 36
SuddenIafolla
Death 18 1994
et al ., J Pediatr 124:409-415,
 Treatment of FAO
Disorders
• Depends on the Fatty Acid Oxidation Defect
• Vitamin/Cofactors
– Carnitine
– Riboflavin
• Diet manipulation
– Avoiding fasting
– Low fat diet High carbohydrate diets
– MCT oils V Long Chain AcylCoA Defects/LCAD
• Transplantation???
• Prevention of intercurrent illness
– Immunizations
– Avoiding ill contacts
• Triheptanoate??
 The 2:00 AM approach to
hypoglycemia
• Age of patient
• When did this occur - first time or repeat
• Why
– Over-utilization
– Underproduction
– Both?
• Stop the hypoglycemia!!
 ED Work-up
• Prioritize: New problem? Critical patient?
Seizing/Combative/Unresponsive?
• Glucose
– <40mg/dl (or <60 mg/dl and symptomatic)
• Get: Cortisol, insulin, growth hormone,
lactate/pyruvate and ABG
• Also get ED7, AST, ALT, GGT, ammonia,
quant. ketones (β -OH butyrate and acetoacetate),
plasma amino acids, acylcarnitine profile, free
fatty acids
• Urine: UA, organic acids and amino acids
 70 Catecholamine and Glucagon Secretion
Blood Glucose concentration mg/dL

60 Cortisol and Growth Hormone Secretion

Autonomic Symptoms
50
Neuroglycopenic Symptoms &
Cognitive Dysfunction
40
Lethargy
30
Seizures and Coma
20

10

0
Hypoglycemic Signs and symptoms
When they crash = Why they crashed

• Fasted for: <1 hr

– Hyperinsulinism – Low free fatty acids (FFA);
High insulin (hyperammonemia)
• 1-6 hrs
– GSD 1, – High FFA with lactic acidosis
gluconeogenesis
• 8-24hrs
– Fatty acid oxidation – High FFA with organic aciduria,
– CPT I abnormal ketone quantitation,
abnormal acylcarnitines, low
(infants/young child) carnitine concentration
 Neonatal Hypoglycemic
Metabolic Disease
• Fatty acid oxidation defect
– Acidosis: – to ++
– Ketosis: NO
– Ammonia: +/- to ++
– Lactate: +/- to ++
• Glycogenosis/Fructose diphosphatase
– Ammonia : normal to +
– Ketones: +
– Lactate +/++
– Ketones: - in type 1; ++ type 3 GSDs
– Other: uric acidemia, elevated triglycerides or
cholesterol
 Neonatal Hypoglycemic
Metabolic Disease continued
• Liver failure?
– Newborn screen?
– Galactosemia
• NH3 nl to +
• No to + acidosis or ketosis
• Lactate + to ++
– DDX
• Tyrosinemia I, neonatal hemochromatosis,
fructosemia, respiratory chain disorders
 Non-neonatal Hypoglycemia
• Fatty acid oxidation defects
• Respiratory chain disease
• Hereditary fructose intolerance
• Organic acidemias
• Gluconeogenic defects
– Fructose diphosphatase, glucose 6-
phosphatase, glycogen synthase
 Metabolic Diseases Can Present as
Hypoglycemia 2
Hepatomegaly Example
– Permanent
• Severe liver failure • Tyrosinemia I
• Cirrhosis • Fructose Intolerance
• Isolated • PEPCK and GSD III,
hepatomegaly fructose diphosphatase
– Without
• Ketoacidosis • organic aciduria
• Acidosis without • HMG-CoA lyase and
ketosis rarely FAO defect
• Ketosis without • Hyperketotic
acidosis hypoglycemia
• Without ketosis • Typical FAOD
 Cardiomyopathy in Infants
• Lysosomal (storage) disorders
• Mitochondrial disorders
• Amino acidopathies
• Organic acidemias
• Fat dysmetabolism and / or carnitine
deficiencies
 Seizures
• Biochemically quiet:
• No acidosis; normal lactate, ketones, glucose and NH3
– Non-ketotic hyperglycinemia
– Sulfite oxidase/ xanthine oxidase
– Pyridoxine dependency
– Peroxisomal disorders
– Glucose transporter defect
– Trifunctional protein defect
• CSF glucose & glycine, pAA, VLCFA, Sulfites,
Trial of pyridoxine
 Nonketotic Hyperglycinemia
• Lethargy, hypotonia, seizures;
characteristic EEG, apnea
• Defect in glycine cleavage
• Glycine is a neurotransmitter
– Classic glycine receptors are inhibitory
– Excitatory neurotransmitter of the N-methyl-
D-aspartate receptor by allosteric modulation
of receptor activity
• Leads to overstimulation of the pathways and
damage
 Won’t Newborn Screening
Solve This?
• Newborn screening is expanded
– But only 28 disorders in Texas
• NBS may not give an answer until after the infant is ill
– Critical window of time
– Turn-around is not fast enough
• NBS will detect
– most of the severe or moderate cases of screened
disorders
• NBS will not detect
– non-screened disorders
– all mild cases of a disorder (later presentations)
 Newborn Screening is not….
• Enough for a diagnosis
– False positives will occur
• Abnormal analyte but no disease
• Fail-safe
– False negatives will occur
• No abnormality for a screened disorder
• As complex to interpret as you thought

• Physicians must still recognize & treat the

infant with an IEM
 ACMG/March of Dimes
List of 29 Disorders for NBS
• 3-Methylcrotonyl-CoA carboxylase
• 3-Methylcrotonyl-CoA carboxylase
deficiency (3MCC)
deficiency (3MCC)
• 3-OH 3-CH3 glutaric aciduria (HMG)
• 3-OH 3-CH3 glutaric aciduria (HMG)
• Argininosuccinic acidemia (ASA)
• Argininosuccinic acidemia (ASA)
• Beta-ketothiolase deficiency (BKT)
• Beta-ketothiolase deficiency (BKT)
• Biotinidase deficiency (BIOT)
• Biotinidase deficiency (BIOT)
• Carnitine uptake defect (CUD)
• Carnitine uptake defect (CUD)
• Citrullinemia (CIT)
• Citrullinemia (CIT)
• •
• Congenital adrenal hyperplasia
(CAH)
• Congenital hypothyroidism
• (HYPOTH)
• Cystic fibrosis (CF)
• Galactosemia (GALT)
• Glutaric acidemia type I (GA I)
• Hb S/Beta-thalassemia (Hb S/Th)
• Hb S/C disease (Hb S/C)
• Hearing
Hearing loss
loss
• Homocystinuria (HCY)
• Isovaleric academia (IVA)
• Long-chain L-3-OH acyl-CoA
dehydrogenase deficiency (LCHAD)
• Maple syrup urine disease (MSUD)
• Medium chain acyl-CoA dehydrogenase
deficiency (MCAD)
Methylmalonic acidemia (Cbl A,B)
• Methylmalonic acidemia (mutase
deficiency) (MUT)
• Multiple carboxylase deficiency (MCD)
• Phenylketonuria (PKU)
•• Propionic acidemia(PKU)
Phenylketonuria (PROP)
• Sickle cell anemia (SCA)
•• Trifunctional protein deficiency
Sickle cell anemia (SCA) (TFP)
• Very long-chain acyl-CoA dehydrogenase
deficiency (VLCAD)
• Tyrosinemia type I (TYR I)
 ‘New’ Disorders - New
Technology
• Expanded group of amino acid diseases
– Phenylketonuria
– Argininosuccinic acidemia (ASA)
– Citrullinemia (CIT)
– Homocystinuria (HCY)
– Tyrosinemia type I (TYR I)
– Maple syrup urine disease (MSUD)
• New group of Organic Acid Disorders
• New group of Fatty Acid Oxidation Disorders

• New / expanded group of Miscellaneous / Other

Screened Disorders
 Interpreting a NBS report
• Added sections
• Amino acids
– Normal or named elevations
– Possible disorder listed
• Acylcarnitine profile
– Identify the abnormal chemical species
– Possible disorders listed
• Biotinidase
 What to do
• Algorithmic approach
• Even a short delay may harm an infant
• Follow the ACT sheet and algorithm
– Find the patient
– Evaluate the patient
– Obtain labs
– Speak with a metabolic geneticist
DSHS
ACT Sheets
What Analyte

PCP’s Actions

Diagnostic
Evaluations

Clinical
Snapshot

More
Information
 Confirmatory Testing
• Some values will be very high
– Metabolic Emergencies requiring immediate
admission
• Intravenous fluids
• May require specialized medications
• Many values will require repeat testing, or
– Acylcarnitine profile
– Urine organic acids
– Plasma amino acids
– Ammonia
– Urine Orotic Acid
 Algorithms

Flow Sheet format

Actions
in shaded boxes
Plasma AC (C8) – high
Urine OA – Normal/high dicarboxylic acids
Urine AG – high hexanoylglycine
Results
in Unshaded box

MCAD Deficiency

http://www.acmg.net/resources/policies/ACT/condition-analyte-links.htm
 Newborn Screening Directory
1-800-252-8023
• Case Management Extensions
• General Information 2129
• Congenital Adrenal Hyperplasia (CAH) 2819
• Congenital Hypothyroidism 3666
• Galactosemia 6827
• Hemoglobinopathies 6832
• Phenylketonuria (PKU) 6827
• Biotinidase Deficiency 2071
• Fatty Acid Disorders, Organic Acid Disorders,
Amino Acid Disorders 7715
 Emergency Medications
• Dextrose
– 10% at a rate of 1.5 x maintenance provides a GIF
high enough to suppress most catabolism
• Alkali
– Sodium bicarbonate to treat acidosis
• Ammonia trapping agents
– IV = Ammonul®
• Combination of sodium benzoate and sodium
phenylacetate
• Needs central line
– Enteral = sodium phenylbutyrate (Buphenyl®)
 Emergency Therapies
• Dialysis
– Needed for extreme hyperammonemia
– For organic acidemias
– To bring amino acid levels down
– Peritoneal vs. hemodialysis/hemofiltration
• Carnitine
– IV 100 – 200 mg/kg/day
– Side effects in large oral doses
– Caution in long chain fatty acid defects
 Vitamin Therapies
• Pyridoxine (Vitamin B6) 100 mg
– Biochemically quiet seizures
– Homocystinuria
• Biotin 10 mg enterally
– Biotinidase defect
– Holocarboxylase synthase
– Pyruvate carboxylase
• Cobalamin (Vitamin B12)
– Methylmalonic acidemia with hyperhomocysteinemia
• Mitochondrial disease
– Niacin, Riboflavin, Coenzyme Q10, Vitamin E, Vitamin C, ++
+
 Patient Known to Have Metabolic Disease?
Yes No ABG
NH3
Type Known ? No Glucose Diagnostic
Yes Ketones
Urea Cycle Defect algorithm
Fatty Acid Defect Lactate
Organic Acidopathy
Storage
Disorder
Lactic Acidosis Emergency Rx Plan
Glycogen Storage
D10+ IVF
Unchanged And if
VS? Treatment plan known? ￪ NH3 NH3 Trapping Agent
Respiratory Acidosis NaHCO3
pattern/rates
Seizures Anticonvulsant
Emesis Yes No Carnitine
CNS status Follow Plan
Physical Exam Hypoketosis
CNS Status Hypoglycemia
Add common Improved Hyperammonemia
sense care Increased Anion Gap
Metabolic Alkalosis
Notify Yes No ? Intubate
Metabolic MD ?IEM ?Toxins
Other lab studies
 Summary
• Consider IEM in your DDX of a sick child
• Five basic lab studies for acute diseases
– Second group of labs often needed
• Treat with glucose
– And correct metabolic derangements
• Special medications for certain disorders
• Known patients may get ill
– Fluids, carbohydrate calories and correction of
physiologic derangements
• Call for help
Some materials in this talk were prepared
using resources provided
by the Carlie Herndon Memorial Fund
ODOR COMPOUND DISORDER
Maple syrup Isoleucine metabolites Maple Syrup Urine Disea
sweet

Musty Phenylacetic acid Phenylketonuria (PKU)

Sweaty feet Isovalerate Isovaleric Acidemia

Cheesy Glutaric Aciduria, type II

Cabbage a-Ketomethylbutyrate Tyrosinemia, type I

Hypermethionemia

Tomcat’s Methylcrotonic acid Methylcrotonic Acidemia

Urine Multiple Carboxylase De

Fishy Trimethylamine, Trimethylaminuria

Carnitine