Disorders of Carbohydrate Metabolism

  • Glycogen Storage Diseases (GSDs):
    • Type I (Von Gierke disease)
    • Type II (Pompe disease)
    • Type III (Cori-Forbes disease)
    • Type IV (Andersen disease)
    • Type V (McArdle disease)
    • Type VI (Hers disease)
    • Type VII (Tarui disease)
    • Type IX (Phosphorylase kinase deficiency)
    • Type 0 (Liver glycogen synthase deficiency)
  • Galactose metabolism disorders:
    • Galactosemia (GALT, GALE, and GALK deficiencies)
  • Fructose metabolism disorders:
    • Hereditary fructose intolerance
    • Fructose-1,6-bisphosphatase deficiency
  • Disorders of gluconeogenesis and glycolysis:
    • Pyruvate kinase deficiency
    • Pyruvate dehydrogenase complex deficiency
  • Lactic acidemia syndromes:
    • Pyruvate carboxylase deficiency
    • Disorders of the Cori cycle

Disorders of Amino Acid Metabolism

  • Phenylalanine metabolism disorders:
    • Phenylketonuria (PKU)
    • Hyperphenylalaninemia
  • Tyrosine metabolism disorders:
    • Tyrosinemia type I (fumarylacetoacetate hydrolase deficiency)
    • Tyrosinemia type II (tyrosine aminotransferase deficiency)
    • Tyrosinemia type III (4-hydroxyphenylpyruvate dioxygenase deficiency)
  • Branched-chain amino acid disorders:
    • Maple syrup urine disease (MSUD)
    • Isovaleric acidemia
    • 3-Methylcrotonyl-CoA carboxylase deficiency
  • Sulfur amino acid disorders:
    • Homocystinuria (cystathionine beta-synthase deficiency)
    • Cystinuria
    • Cystinosis
  • Other amino acid metabolism disorders:
    • Argininosuccinic aciduria
    • Non-ketotic hyperglycinemia (glycine encephalopathy)
    • Histidinemia
    • Hyperprolinemia (types I and II)

Disorders of Organic Acid Metabolism

  • Short-chain organic acidemias:
    • Propionic acidemia
    • Methylmalonic acidemia
    • Isovaleric acidemia
  • Dicarboxylic acidemias:
    • Glutaric acidemia type I
    • 3-Hydroxy-3-methylglutaryl-CoA lyase deficiency (HMG-CoA lyase deficiency)
    • Malonic acidemia
  • Multiple carboxylase deficiency:
    • Biotinidase deficiency
    • Holocarboxylase synthetase deficiency

Disorders of Lipid Metabolism

  • Fatty Acid Oxidation Disorders:
    • Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency
    • Very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency
    • Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency
    • Carnitine palmitoyltransferase deficiencies (CPT1 and CPT2)
    • Carnitine transporter defect
  • Peroxisomal disorders:
    • Zellweger spectrum disorders
    • Adrenoleukodystrophy
    • Refsum disease
  • Lysosomal lipid storage diseases:
    • Gaucher disease
    • Niemann-Pick disease types A, B, and C
    • Farber lipogranulomatosis
    • Wolman disease
    • Cholesteryl ester storage disease
  • Sphingolipidoses:
    • Tay-Sachs disease
    • Sandhoff disease
    • Krabbe disease
    • Fabry disease
    • Metachromatic leukodystrophy

Disorders of Energy Metabolism

  • Mitochondrial respiratory chain disorders:
    • MELAS (Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes)
    • Leigh syndrome
    • MERRF (Myoclonic epilepsy with ragged red fibers)
    • NARP (Neuropathy, ataxia, and retinitis pigmentosa)
    • Kearns-Sayre syndrome
  • Coenzyme Q10 deficiency
  • Pyruvate dehydrogenase complex deficiency
  • Krebs cycle enzyme deficiencies:
    • Fumarase deficiency
    • Succinate dehydrogenase deficiency

Disorders of Purine and Pyrimidine Metabolism

  • Purine metabolism disorders:
    • Lesch-Nyhan syndrome (HGPRT deficiency)
    • Adenine phosphoribosyltransferase deficiency
    • Xanthinuria
    • Adenylosuccinate lyase deficiency
  • Pyrimidine metabolism disorders:
    • Dihydropyrimidine dehydrogenase deficiency
    • Orotic aciduria

Disorders of Vitamin and Cofactor Metabolism

Disorders of Thiamine (Vitamin B1) Metabolism

  • Thiamine-responsive megaloblastic anemia (TRMA)
  • Biotin-thiamine-responsive basal ganglia disease (BTBGD)
  • Maple syrup urine disease (MSUD) (thiamine-responsive variant)
  • Wernicke-Korsakoff syndrome (acquired thiamine deficiency)
  • Beriberi (dry and wet forms—acquired deficiency)

Disorders of Riboflavin (Vitamin B2) Metabolism

  • Multiple acyl-CoA dehydrogenase deficiency (MADD, Glutaric Aciduria type II)
  • Riboflavin transporter deficiency (formerly Brown-Vialetto-Van Laere syndrome & Fazio-Londe disease)
  • Riboflavin-responsive mitochondrial disorders

Disorders of Niacin (Vitamin B3) Metabolism

  • Pellagra (acquired niacin deficiency)
  • Hartnup disease (impaired tryptophan absorption/conversion)

Disorders of Pyridoxine (Vitamin B6) Metabolism

  • Pyridoxine-dependent epilepsy (ALDH7A1 deficiency)
  • Pyridoxal phosphate-responsive seizures (PNPO deficiency)
  • Hypophosphatasia (alkaline phosphatase deficiency)
  • Pyridoxine-responsive sideroblastic anemia

Disorders of Biotin (Vitamin B7) Metabolism

  • Biotinidase deficiency
  • Holocarboxylase synthetase deficiency
  • Biotin transporter deficiency (biotin-responsive basal ganglia disease)

Disorders of Folate (Vitamin B9) Metabolism

  • Hereditary folate malabsorption (SLC46A1 mutation)
  • Cerebral folate deficiency syndrome (CFD)
  • Methylenetetrahydrofolate reductase (MTHFR) deficiency
  • Glutamate formiminotransferase-cyclodeaminase deficiency (FTCD)
  • Dihydrofolate reductase (DHFR) deficiency

Disorders of Vitamin B12 (Cobalamin) Metabolism

  • Intrinsic factor deficiency (congenital pernicious anemia)
  • Imerslund-Gräsbeck syndrome (cobalamin absorption defect)
  • Transcobalamin deficiency
  • Methylmalonic acidemia (MMA) (Cbl A, B, C, D, F disorders)
  • Combined methylmalonic acidemia and homocystinuria (CblC, CblD, CblF, CblJ)
  • Adenosylcobalamin deficiency
  • Methylcobalamin deficiency

Disorders of Ascorbic Acid (Vitamin C) Metabolism

  • Scurvy (acquired deficiency)
  • Vitamin C transporter deficiency (SLC23A1/SLC23A2 mutations)

Disorders of Vitamin A Metabolism

  • Vitamin A deficiency (xerophthalmia, night blindness)
  • Hypervitaminosis A
  • Congenital disorders of retinoid metabolism

Disorders of Vitamin D Metabolism

  • Vitamin D-dependent rickets Type 1A (CYP27B1)
  • Vitamin D-dependent rickets Type 1B (CYP2R1)
  • Vitamin D-dependent rickets Type 2A (VDR deficiency)
  • Vitamin D-dependent rickets Type 2B (hormone response element defect)

Disorders of Vitamin E Metabolism

  • Ataxia with vitamin E deficiency (AVED)
  • Familial isolated vitamin E deficiency (FIVE)
  • Abetalipoproteinemia (malabsorption syndrome)

Disorders of Vitamin K Metabolism

  • Vitamin K deficiency bleeding (VKDB)
  • Combined deficiency of vitamin K-dependent coagulation factors (VKCFD)
  • Gamma-glutamyl carboxylase deficiency (GGCX)
  • Vitamin K epoxide reductase deficiency (VKOR)

Disorders of Coenzyme Q10 Metabolism

  • Primary Coenzyme Q10 deficiency (COQ2, COQ4, COQ6, COQ8A/ADCK3)
  • Secondary CoQ10 deficiency

Disorders of Carnitine Metabolism

  • Primary systemic carnitine deficiency (SLC22A5)
  • Carnitine palmitoyltransferase I deficiency (CPT1)
  • Carnitine palmitoyltransferase II deficiency (CPT2)
  • Carnitine-acylcarnitine translocase deficiency (CACT)

Disorders of Creatine Metabolism

  • Guanidinoacetate methyltransferase (GAMT) deficiency
  • Arginine-glycine amidinotransferase (AGAT) deficiency
  • Creatine transporter defect (SLC6A8)

Disorders of Alpha-Lipoic Acid Metabolism

  • Lipoic acid synthetase deficiency (LIAS)
  • Lipoyltransferase 1 deficiency (LIPT1)
  • Lipoyltransferase 2 deficiency (LIPT2)
  • Pyruvate dehydrogenase complex defects (lipoic acid metabolism)

Disorders of Tetrahydrobiopterin (BH4) Metabolism

  • GTP cyclohydrolase I deficiency (GCH1, dopa-responsive dystonia)
  • 6-Pyruvoyl-tetrahydropterin synthase deficiency (PTPS)
  • Sepiapterin reductase deficiency (SPR)
  • Dihydropteridine reductase deficiency (DHPR)
  • Pterin-4-alpha-carbinolamine dehydratase deficiency (PCD)

Disorders of Copper Metabolism

  • Wilson’s disease (ATP7B)
  • Menkes disease (ATP7A)
  • Occipital horn syndrome (ATP7A partial deficiency)

Disorders of Iron Metabolism

  • Aceruloplasminemia
  • Hereditary hemochromatosis

Disorders of Selenium Metabolism

  • SECISBP2 deficiency
  • Congenital deficiency of selenoproteins

Disorders of Urea Cycle Metabolism

  • Primary urea cycle disorders:
    • Carbamoyl phosphate synthetase I (CPSI) deficiency
    • Ornithine transcarbamylase (OTC) deficiency
    • Argininosuccinate lyase deficiency
    • Argininosuccinate synthetase deficiency (Citrullinemia type I)
    • Arginase deficiency (Argininemia)
  • Secondary urea cycle disorders:
    • N-acetylglutamate synthase (NAGS) deficiency

Lysosomal Storage Disorders

  • Mucopolysaccharidoses (MPS):
    • Hurler syndrome (MPS I)
    • Hunter syndrome (MPS II)
    • Sanfilippo syndrome (MPS III)
    • Morquio syndrome (MPS IV)
    • Maroteaux-Lamy syndrome (MPS VI)
    • Sly syndrome (MPS VII)
  • Oligosaccharidoses:
    • Mannosidosis
    • Fucosidosis
    • Schindler disease
  • Neuronal ceroid lipofuscinoses (NCLs):
    • CLN1 (Infantile)
    • CLN2 (Late infantile)
    • CLN3 (Juvenile Batten disease)
  • Niemann-Pick disease 

Disorders of Neurotransmitter Metabolism

  • Catecholamine and serotonin metabolism disorders:
    • Tyrosine hydroxylase deficiency
    • Aromatic L-amino acid decarboxylase (AADC) deficiency
  • GABA metabolism disorders:
    • Succinic semialdehyde dehydrogenase deficiency
  • Monoamine oxidase (MAO) deficiency
  • Pterin metabolism disorders:
    • Tetrahydrobiopterin (BH4) deficiency

Disorders of Cholesterol and Sterol Metabolism

  • Cholesterol synthesis disorders:
    • Smith-Lemli-Opitz syndrome (SLOS)
    • Lathosterolosis
    • Desmosterolosis
  • Sterol transport disorders:
    • Niemann-Pick type C
    • Sitosterolemia