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| Enzyme Disorders | ||||
|---|---|---|---|---|
| Condition | Deficiency | Labs | Key Features | |
| Amino Acid Disorders | ||||
| Phenylketonuria (PKU) | Phenylalanine hydroxylase | ↑ phenylalanine, ↓ tyrosine, positive Guthrie test | Musty odor Intellectual disability fair skin |
aR |
| Alkaptonuria | Homogentisate oxidase | ↑ homogentisic acid in urine (darkens with air) | Ochronosis, arthritis | aR |
| Homocystinuria | Cystathionine β-synthase deficiency (or impaired B6 metabolism) | ↑ homocysteine in urine & plasma, normal methylmalonic acid | Marfanoid habitus, intellectual disability, thrombosis, downward lens subluxation | aR |
| Cystinuria | Defective renal PCT transporter for COLA amino acids (Cystine, Ornithine, Lysine, Arginine) | Hexagonal crystals, positive cyanide-nitroprusside test | Recurrent hexagonal kidney stones | aR |
| Maple Syrup Urine Disease | Branched-chain α-ketoacid dehydrogenase | ↑ branched-chain amino acids in plasma and urine | Sweet-smelling urine, poor feeding, lethargy | aR |
| Propionic Acidemia | Propionyl-CoA carboxylase | ↑ propionic acid, metabolic acidosis, ↑ ammonia | Vomiting, hypotonia, metabolic acidosis | aR |
| Methylmalonic Acidemia | Methylmalonyl-CoA mutase | ↑ methylmalonic acid, metabolic acidosis, ↑ ammonia | Metabolic acidosis, hypoglycemia, hypotonia | aR |
| Hartnup Disease | Neutral amino acid transporter defect (SLC6A19) | ↑ neutral amino acids in urine | Niacin deficiency (pellagra-like), ataxia, photosensitivity | aR |
| Urea Cycle Disorders | ||||
| Carbamoyl Phosphate Synthetase I Deficiency | Carbamoyl phosphate synthetase I | ↑ ammonia, normal orotic acid | Hyperammonemia, vomiting, no orotic aciduria | aR |
| Ornithine Transcarbamylase (OTC) Deficiency | Ornithine transcarbamylase | ↑ ammonia, ↑ orotic acid, no acidosis | Hyperammonemia, ↑ orotic acid, no acidosis | X-linked |
| Carbohydrate Disorders | ||||
| Galactokinase Deficiency | Galactokinase | Galactosemia, galactosuria, reducing sugars in urine | Infantile cataracts, galactose in blood and urine, no hepatomegaly | aR |
| Galactosemia (Classic) | Galactose-1-phosphate uridyltransferase | ↑ galactose-1-phosphate, positive Clinitest | Jaundice, hepatomegaly, cataracts, E. coli sepsis | aR |
| Hereditary Fructose Intolerance | Aldolase B | Hypoglycemia, ↑ uric acid, reducing sugars in urine | Vomiting, hypoglycemia after fruit intake | aR |
| Essential Fructosuria | Fructokinase | Benign galactosuria, positive reducing sugar test | Benign, asymptomatic, reducing sugar in urine | aR |
| Fructose-1,6-bisphosphatase Deficiency | Fructose-1,6-bisphosphatase | Metabolic acidosis, hypoglycemia, ↑ lactate | Fasting hypoglycemia, lactic acidosis, ketosis | aR |
| Pyruvate Kinase Deficiency | Pyruvate kinase | Hemolytic anemia, ↑ 2,3-BPG, ↑ reticulocytes | Hemolytic anemia, splenomegaly, ↑ 2,3-BPG | aR |
| Lysosomal Storage Disorders | ||||
| Tay-Sachs Disease | Hexosaminidase A deficiency ⬆︎ GM2 buildup |
↓ hexosaminidase A activity, normal liver function | Cherry-red spot | aR |
| Fabry Disease | α-galactosidase A deficiency ⬆︎ globotriaosylceramide |
↑ globotriaosylceramide in urine, proteinuria | Angiokeratomas, Neuropathy, Renal failure | X-linked |
| Gaucher Disease | β-glucocerebrosidase deficiency ⬆︎ glucocerebroside |
“Crinkled paper” macrophages, pancytopenia | Hepatosplenomegaly, bone crises, pancytopenia, lipid-laden macrophages | aR |
| Krabbe Disease | Galactocerebrosidase deficiency ⬆︎ galactocerebroside, psychosine |
Globoid cells in brain, ↑ psychosine | Peripheral neuropathy, developmental delay, optic atrophy, globoid cells | aR |
| Niemann-Pick Disease | Sphingomyelinase deficiency ⬆︎ sphingomyelin |
Foamy macrophages, ↓ sphingomyelinase | Progressive neurodegeneration, Hepatosplenomegaly, Cherry-red macula | aR |
| Hunter Syndrome | Iduronate sulfatase deficiency ⬆︎ Dermatan sulfate, Heparan sulfate |
↑ dermatan & heparan sulfate in urine | Mild Hurler features, aggressive behavior no corneal clouding |
X-linked |
| Hurler Syndrome | α-L-iduronidase deficiency ⬆︎Dermatan sulfate, ⬆︎ Heparan sulfate |
↑ dermatan & heparan sulfate in urine | Developmental delay, gargoylism, airway obstruction, corneal clouding | aR |
| Purine & Pyrimidine Disorders | ||||
| Lesch-Nyhan Syndrome | HGPRT deficiency ⬆︎ excess uric acid and purine salvage dysfunction |
↑ uric acid, orange sand in diaper | Self-mutilation, gout, dystonia, chorea | X-linked |
| Orotic Aciduria | UMP synthase deficiency | ↑ orotic acid, megaloblastic anemia, no hyperammonemia | Megaloblastic anemia not responsive to B12/folate, orotic acid in urine, no hyperammonemia | aR |
| Adenosine Deaminase Deficiency (SCID) | ADA (Adenosine deaminase) | ↓ ADA activity, ↑ dATP, lymphopenia | SCID phenotype, ↑ dATP toxic to lymphocytes | aR |
| Glycogen Storage Diseases | ||||
| Von Gierke Disease (Type I) | Glucose-6-phosphatase | Severe fasting hypoglycemia, ↑ lactate, ↑ uric acid | Severe fasting hypoglycemia, hepatomegaly | aR |
| Pompe Disease (Type II) | Lysosomal acid α-1,4-glucosidase (acid maltase) | ↑ glycogen in lysosomes, cardiomegaly on imaging | Cardiomegaly, hypotonia, exercise intolerance | aR |
| Cori Disease (Type III) | Debranching enzyme (α-1,6-glucosidase) | ↑ limit dextrin structures in cytosol | Milder fasting hypoglycemia, no lactic acidosis | aR |
| McArdle Disease (Type V) | Muscle glycogen phosphorylase | Flat venous lactate curve with exercise | Muscle cramps, myoglobinuria after exercise | aR |
| Andersen Disease (Type IV) | Branching enzyme | ↑ liver enzymes, cirrhosis on biopsy | Hepatosplenomegaly, failure to thrive, progressive cirrhosis | aR |
| Hers Disease (Type VI) | Hepatic glycogen phosphorylase | ↑ glycogen in liver, mild hypoglycemia | Hepatomegaly, mild fasting hypoglycemia, growth delay | aR |
| Tarui Disease (Type VII) | Muscle phosphofructokinase (PFK-1) | ↑ glycogen in muscle, ↓ PFK-1 activity | Exercise intolerance, muscle cramps, hemolytic anemia | aR |
| Fatty Acid Disorders | ||||
| MCAD Deficiency | Medium-chain acyl-CoA dehydrogenase | Hypoketotic hypoglycemia, ↑ dicarboxylic acids | Vomiting, sudden death in infants | aR |
| Peroxisomal Disorders | ||||
| Refsum Disease | Impaired alpha-oxidation (peroxisomal disorder) | ↑ phytanic acid | Scaly skin, ataxia, night blindness, shortening of 4th toe | aR |
| Zellweger Syndrome | Peroxisome biogenesis defect (PEX gene) | ↑ VLCFAs, ↓ plasmalogens | Hypotonia, seizures, hepatomegaly, early death | aR |
| Adrenoleukodystrophy | Defective β-oxidation of very long-chain fatty acids (VLCFA) | ↑ VLCFAs in plasma | Adrenal crisis, progressive CNS demyelination | X-linked |
| Familial Dyslipidemias | ||||
| Type I Hyperchylomicronemia | Lipoprotein lipase or ApoC-II deficiency | ↑ chylomicrons, ↑ TG, creamy supernatant | TG accumulation, recurrent pancreatitis | aR |
| Type IIa Familial Hypercholesterolemia | LDL receptor or ApoB-100 deficiency | ↑ LDL, normal TG | ↑ LDL, tendon xanthomas, corneal arcus | AD |
| Type IIb Combined Hyperlipidemia | LDL receptor or ApoB-100 defect + ↑ VLDL | ↑ LDL, ↑ VLDL, ↑ TG | ↑ LDL + VLDL, tendon xanthomas, corneal arcus | AD |
| Type III Dysbetalipoproteinemia | ApoE deficiency | ↑ chylomicrons, ↑ remnants, ↑ cholesterol | ↑ chylomicrons + VLDL remnants, palmar xanthomas | aR |
| Type IV Hypertriglyceridemia | Hepatic VLDL overproduction | ↑ VLDL, ↑ TG | ↑ VLDL, hypertriglyceridemia, pancreatitis | AD |
| Abetalipoproteinemia | Deficiency of ApoB-48 & ApoB-100 (MTP gene) | ↓ ApoB, ↓ chylomicrons, acanthocytosis | No chylomicrons, VLDL, or LDL fat malabsorption, ↓ vitamin E |
aR |
| “1 LP, 2 LD, b adds V, 3 is E, 4 gets more” | ||||