Topic Disease defect Symptoms Genetic

inheritance
ETC Fatal infantile mitochondria Oxidoreductases deficiency generalized weakness, lactic acidosis, require assisted Autosomal
myopathy and renal dysfunction cytochrome c oxidase deficiency ventilation recessive
Mitochondrial myopathy defect in complex 1 or Lactic acidosis, stroke, generalized weakness Autosomal
encephalopathyl lactic acidosis cytochrome oxidase Recessive
and stroke
Glycogen Type 1 (von gierks disease) deficiency of Glucose 6 glycogen, hypoglycemia, lactacidemia, ketosis, Autosomal
metabolism phosphatase hepatomegally hyperlipidemia, hyperuricemia Recessive
Type 2 (Pompe’s disease) deficiency of lysosomal alpha 1- fatal and associated with accumulation of glycogen in Autosomal
4 and alpha 1-6 glucosidase lysosomes, heart failure Recessive
(acid maltase)
Type III (limit dextrinosis, Forbes’ deficiency of the debranching accumulation of short branches glycogen (dextrin), mild Autosomal
disease or Cori’s disease) enzyme hypoglycemia Recessive
Type IV Amylopectinosis, absence of the branching Accumulation of non branched glycogen…death in the first Autosomal
Andersen’s disease enzyme year due to cardiac or liver failure Recessive
Type V Myophosphorylase absence of muscle diminished exercise tolerance, muscles have high contents of Autosomal
deficiency, McArdle’s disease phosphorylase normal glycogen, little or no lactate in the blood after Recessive
exercise
Type VI Hers’ disease deficiency of liver high contents of glycogen in the liver, mild hypoglycemia Autosomal
phosphorylase Recessive

Type VII Tarui’s disease deficiency of diminished exercise tolerance, muscles have high contents of Autosomal
phosphofructokinase 1 in the normal glycogen, little or no lactate in the blood after Recessive
muscle and erythrocyte exercise, sometimes associated with hemolytic anemia
Type VIII deficiency of liver high contents of glycogen in the liver, mild hypoglycemia X-linked
phosphorylase kinase
PPP glucose-6-phosphate glucose-6-phosphate hemolytic anemia X- linked
dehydrogenase dehydrogenase deficiency recessive
Fructose Essential fructosuria lack of fructokinase present in fructosuria Autosomal
metabolism the liver, pancreatic islets and Recessive
kidney cortex
Hereditary fructose intolerance lack of aldolase B vomiting, poor feeding, jaundice, hepatomegaly, hemorrhage Autosomal
and eventually hepatic failure and death.following fructose Recessive
intake
Hereditary fructose-1,6- Hereditary fructose-1,6- hypoglycemia, Autosomal
bisphosphatase deficiency bisphosphatase deficiency apnea, hyperventillation, Recessive
ketosis and lactic acidosis
Galactose Classic galactosemia type 1 galactose-1-phosphate uridyl failure of neonates to thrive. Autosomal
Metabolism transferase Vomiting and diarrhea occur following ingestion of milk, Recessive
hence individuals are termed lactose intolerant.
 Classic galactosemia type 2
galactokinase failure of neonates to thrive.Vomiting and diarrhea occur Autosomal
following ingestion of milk, hence individuals are termed Recessive
lactose intolerant. impaired liver function (which if left
untreated leads to severe cirrhosis
Elevated blood galactose, galactosemia,metabolic acidosis,
blindness (formation of galactitol), cataracts
Urinary galactitol, & hyperaminoaciduria

UDP-galactose-4-epimerase UDP-galactose-4-epimerase Type 1 benign affecting only red and white blood cells Autosomal
deficiency Type 2 affects multiple tissues and manifests symptoms Recessive
similar to the transferase deficiency
Fatty acid carnitine deficiency in preterm carnitine deficiency episodic periods of hypoglycemia due to reduced Autosomal
oxidation infants, in hemodialysis, patients gluconeogensis Recessive
with organic aciduria
inherited CPT-I deficiency affects inherited CPT-I deficiency resulting in reduced fatty acid oxidation and ketogenesis with Autosomal
only the liver hypoglycemia Recessive
CPT-II affects primarily skeletal CPT-II deficiency weakness, necrosis, myoglobinuria Autosomal
muscles Recessive
long chain 3-hydroxyacylCoA DH Deficiency of long chain 3- acute fatty liver of pregnancy Autosomal
hydroxyacylCoA DH Recessive
Autosomal
Recessive
Jamaican vomiting sickness inactivates medium and short resulting in reduced fatty acid oxidation and ketogenesis with Autosomal
chain acylCoA DH hypoglycemia Recessive
Autosomal
Recessive
dicarboxylic aciduria lack of mitochondrial medium excretion of C6—C10 omega-dicarboxylic acids and by Autosomal
chain acylCoA DH nonketotic hypoglycemia Recessive
Refsum ‘s disease Accumulation of phytanic acid… resulting in reduced fatty acid oxidation and ketogenesis with Autosomal
metyl hypoglycemia Recessive
oxidation…defect in alpha
oxidation which removes the
methy group
Zellweger’s syndrome(cerebro- peroxisomes deficiency in all Autosomal
hepatorenal tissues Recessive
sphingolipidosis Tay sachs d. hexosaminidase Mental retardation, blindness, muscular weakness.
Fabry’s d. α- galactosidase Skin rash, kidney failure (full symptoms only in males ;x-lined
recessive).
Metachromatic leukodystrophy arylsulfatase Mental retardation and psycho logic disturbance in adults ;
 dyemilination.
Krabbe’s d. Β-galactosidase Mental retardation, myelin almost absent.
Gaucher’s d. B-galactosidase Enlarged liver and spleen, erosion of long bones, mental
retardation in infants .
Niemman pick d. sphingomyelinase Enlarged liver and spleen, mental retardation in early life.
Farber’s d. ceramidase Hoaresness, dermatitis, skeletal deformation, mental
retardation in early life.
Primary Abetalipoproteinemia No CM, VLDL or LDL low blood level of
disorders are formed because acylglycerols which
of the of defect of TAG accumulate in the liver and
plasma transport protein intestine. causes
lipoprote which prevents the malabsorption and early
ins loading of apo B with death
the lipid.

familial LDL concentration is Healthy individuals and

hypobetalipoproteinemia 10-60% of normal. long-lived
Apo B proteins (100,
48) are present.
Chylomicroms are
normal.
.

Familial alpha-lipoprotein Very low or nearly Atherosclerosis in the

deficiency (Tangier absent HDL. elderly
disease, Fish-eye disease, CM, VLDL are normal
or Apo AI deficiencies
familial LPL deficiency High TAG. Associated with
Type I deficiency of LPL or
abnormal LPL, or apo CII
deficiency.
Slow clearance of CM and
VLDL.
Low levels of LDL and HDL
Familial Type IIa due to reduced LDL clearance, high
hypercholesterolemia defective LDL LDL, hypercholesterolemia,
Type II receptor or mutation atherosclerosis and
in the ligand binding coronary heart disease
region.
Type IIb tendency of
VLDL to be elevated.

Wolman’s disease Deficiency in Reduced clearance of LDL…

(cholesteryl ester storage cholesteryl ester atherosclerosis
disease) hydrolase in
lysosomes
Familial type III Defect in remnant associated with increased
hyperlipoproteinemia clearance by the liver CM and VLDL remnants.
(remnant removal disease due to abnormality in It results in
apo E hypercholesterolemia
 Familial Overproduction of Hypercholesterolemia
hypertriacylglycerolemia VLDL…
Type IV: hyperinslinemia

Familial type V High CM andVLDL

hyperlipoproteinemia Defect LPL or apo CII
High TAG and C with
low LDL and HDL
Familial Increased HDL GOOD
hyperalphalipoproteinemi
a
Hepatic lipase deficiency Hepatic lipase Accumulation of TAG
deficiency remnants of HDL and VLDL

Familial LCAT deficiency LCAT deficiency blocks reverse transport of

C.
HDL remains as discoid
Low level of plasma CE and
lysophospholipids

Familial lipoprotein (a) LDL attached to apo Premature coronary heart

excess A. disease due to
atherosclerosis

Purine Gout Prppsynthase Overactivity(↑ X – linked

Metaboli V max) recessive
sm Gout Prpp synthase Resistance to feedback x-linked
inhibtion recessive
Gout PRPP Synthase Low Km for ribose-5-p X- linked
recessive
Gout HGPRT ase Partial deficiency X – linked
recessive
Lesch-Nyhan syndrome HGPRT ase Complete deficiency X – linked
recessive
Immunodeficiency Adenosine Deaminase Severe deficiency Autosomal
recessive
X anthinuria X anthine oxidase Complete deficiency Autosomal
recessive
Pyrimidi Type (I) orotic aciduria Deficiency of both Patients present with Autosomal
ne orotate retarded growth, recessive
metaboli phosphoribosyl Megaloblastic anaemia (No
sm transferase and folate or B12 deficiency),
 orotidylate leucopenia.
decarboxylase Defect in DNA synthesis.
Type (II) Orotic aciduria Deficiency of Megaloblastic anaemia Autosomal
orotidylate recessive
decarboxylase
Urea Hyperammonemia typeI carbamoyl phosphate vomiting, avoidance of high autosomal
cycle synthetase protein diets, intermittent recessive
ataxia, irritability, lethargy,
and mental retardation
hyperammonemia typeII ornithine vomiting, avoidance of high X linked defect
transcarbamoylase protein diets, intermittent
ataxia, irritability, lethargy,
and mental retardation
elevated level of glutamine
in the blood,cerebrospinal
fluid and urine
citrullinemia in argininosuccinate vomiting, avoidance of high recessive
synthase. protein diets, intermittent inherited
ataxia, irritability, lethargy, disorder
and mental retardation
argininosuccinicaciduria argininosuccinase vomiting, avoidance of high recessive
protein diets, intermittent inherited
ataxia, irritability, lethargy, disorder
and mental retardation
hyperargininemia arginase vomiting, avoidance of high autosomal
protein diets, intermittent recessive
ataxia, irritability, lethargy,
and mental retardation
Carbon Hyperprolinemia I Deficiency of proline Mental retardation occurs in Autosomal
skeleton DH half of the patients. recessive
metaboli
sm
Hyperprolinemia type II: Due to deficiency of It affects both proline and autosomal
G-δ-semialdehyde HP catabolism recessive
DH.
Gyrate atrophy of the deficiency of chorioretinal degeneration autosomal
retina ornithine-б- with progressive loss of recessive
transaminase peripheral vision, tunnel
vision, and ultimately
blindness. High ornithine
Hyperornithinemia Ornithine citrulline autosomal
hyperammonemia antiporter defect recessive
syndrome
Histidinemia
Urocanic aciduria
Glycinuria
Primary hyperoxaluria
Cystinuria (cystine-
lysinuria)
Cystinosis (cystine storage
disease
Homocystinuria type I
Homocystinuria type II
deficiency of histidase benign condition. 1:11500, autosomal
enzyme elevated blood and urine recessive
histidine
urocanase increased excretion of autosomal
urocanate in urine. It is recessive
benign condition
the defect is in renal characterized by excretion autosomal
tubular reabsorption of 0.6-1 g of glycine per day recessive
and a tendency to form
oxalate renal stones.
However, glycine levels in
the blood are normal and it
is thought that
excessive excretion of autosomal
urinary oxalate unrelated to recessive
dietary intake progressive
bilateral calcium oxalate
urolithiasis,
nephrocalcinosis, recurrent
infection of urinary tract
which usually lead to death
from renal failure or
hypertension
defect is in renal autosomal
tubular reabsorption recessive
for cystine
lysine, arginine and
ornithine
lysosomal disorder Cystine crystals are autosomal
characterized by deposited in tissues and recessive
defective carrier organs, particularly in the
mediated transport of reticuloendothelial system
cystine. Cystinosis is usually
associated with generalized
aminoaciduria. Other renal
functions are impaired and
patients usually die young
from acute renal failure
cystathionine β-
synthase
N5,N10 autosomal
methylenetetrahydrof recessive
olate reductase
Homocystinuria type III low N5 – autosomal
methyltetrahydrofola recessive
te-homocysteine
transmethylase
Homocystinuria type IV N5 – autosomal
methyltetrahydrofola recessive
te-homocysteine
transmethylase
Hypermethioninemia methionine autosomal
adenosyltransferase recessive
Cystathioninuria cystathionase autosomal
recessive
Sulfituria (sulfocysteinuria sulfite oxidase autosomal
(desulfinase recessive
3 mercaptopyruvate- 3-MP autosomal
cysteine disulfiduria sulfurtransferase recessive
deficiency
hyperphenylalaninemia defects in associated with mental autosomal
type I or classic phenylalanine retardation, seizures, recessive
phenylketonuria hydroxylase psychoses, eczema and a
mousy odor Alternative
catabolites are
phenyllactate,
phenylacetate and
phenylacetylglutamine
hyperphenylalaninemia defects in autosomal
type II and III dihydrobiopterin recessive
reductase
hyperphenylalaninemia defects in autosomal
type IV and V dihydrobiopterin recessive
biosynthesis
tyrosinemia type I fumaryacetoacetate infants exhibit diarrhea, autosomal
(tyrosinosis) hydrolase vomiting, cabbage-like odor recessive
and fail to thrive. They die
of liver failure in 6-8months
if not treated
tyrosinemia type II
(Richner-Hanhart
syndrome)
Neonatal tyrosinemia
Alkaptonuria
(ochronosis) and artheritis
Maple syrup urine disease
(branched chain
ketonuria)
Intermittent branched-
chain ketonuria
Isovaleric acidemia
liver tyrosine Eye, skin lesions and autosomal
transaminase moderate mental recessive
retardation
Urinary metabolites include
PHPP, PHPlactate,
PHPacetate, N-
acetyltyrosine and tyramine
PHPP hydroxylase high blood levels of Tyr and autosomal
Phe. High level of urinary recessive
tyrosine, PHPLactate, N-
acetyl tyrosine and
tyramine.
Homogentisate Darkening of urine exposed autosomal
oxidase to air Generalized recessive
pigmentation of connective
tissue
Ochronosis results from oxidation of homogentisate autosomal
by polyphenol oxidase, forming benzoquinone recessive
acetate which polymerizes and binds to connective character
tissue macromlecules
Homogentisate in urine is oxidized to a brownish-
black pigment.
α-ketoacid Urine odor resembles that autosomal
decarboxylase of maple syrup or burnt recessive
deficiency sugar difficulty in feeding,
vomiting, lethargy
Extensive brain damage
occur in surviving children
and death usually occur by
the end of the first year
structural Symptoms occur late in life autosomal
modifications of the and only intermittently with recessive
a-keto acid good prognosis on dietary
decarboxylase control
isovaleryl-CoA Isovalerate in sweat and autosomal
dehydrogenase urine Cheesy odor of the recessive
(Leucine catabolism) breath and body fluids
 Vomiting, acidosis, and
coma

Methylmalonic aciduria deficiency of vitamin Vomiting, acidosis, and autosomal

(valine and isoleucine B12 coma recessive

Propionic acidemia Propionyl Co A High blood level of autosomal

carboxylase propionate recessive
deficiency
Periodic hyperlysinemia competitive inhibition vomiting, avoidance of high autosomal
with associated of arginase protein diets, intermittent recessive
hyperammonemia ataxia, irritability, lethargy,
and mental retardation
Persistent hyperlysinemia deficiency in sacch DH autosomal
without recessive
hyperammonemia
Hartnup disease intestinal and renal Signs include a general autosomal
transport of neutral neutral aminoaciduria and recessive
amino acids, including increased excretion of
W indole derivatives pellagra
like symptoms