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genetic metabolic diseases

Monday 19 April 2004

Inborn errors of metabolism are characterized by dysregulation of the metabolic networks that underlie development and homeostasis, and constitute an important and expanding group of genetic disorders in humans.

Types (summary)

- Disorders of carbohydrate metabolism

  • E.g., glycogen storage disease (E74.0)

- Disorders of amino acid metabolism

- Disorders of organic acid metabolism (organic acidurias)

  • E.g., alcaptonuria (E70.2)

- Disorders of fatty acid oxidation and mitochondrial metabolism

  • E.g., medium chain acyl dehydrogenase deficiency (glutaric acidemia type 2)

- Disorders of porphyrin metabolism

  • E.g., acute intermittent porphyria (E80.2)

- Disorders of purine or pyrimidine metabolism

  • E.g., Lesch-Nyhan syndrome (E79.1)

- Disorders of steroid metabolism

- Disorders of mitochondrial function

- Disorders of peroxisomal function

  • E.g., Zellweger syndrome (Q87.8)

- Lysosomal storage disorders

Types (developed)

I. Defects in metabolism of amino acids

- Phenylalanine
- Tyrosine metabolism defects

  • tyrosinemia type I
  • tyrosinemia type II
  • transient tyrosinemia of the newborn
  • hawkinsinuria
  • albinism
  • alcaptonuria

- Sulfur-containing amino acids metabolism defects

  • homocystinemia (homocystinuria)
    • homocystinemia type I
    • homocystinemia type II
    • homocystinemia type III
  • methionine
  • hypermethioninemia
  • cystathioninemia
  • cysteine/cystine
  • cystinuria
  • cystinosis
  • sulfite oxidase deficiency
  • beta-mercaptolate-cysteine disulfiduria
  • taurinuria

- Tryptophane

  • Hartnup disease
  • serotonin deficiency
  • tryptophanemia
  • kynureninuria
  • kynureninase defects - hydroxykynureninuria
  • pyridoxine-responsive xanthurenic aciduria
  • organic acidemias
    • indicanuria - tryptophane malapsorption
    • hydincuria
    • indolylacroylglycynuria
    • glutaric aciduria type 1

- valine, leucine, isoleucine and related organic acidemias
- glycine
- serine
- threonine
- proline - hydroxyproline
- glutamic acid
- urea cycle (hyperammonemia) (arginine, citrulline, ornithine)

  • déficit en ornithine transcarbamylase
  • déficit en carbamyl phophate synthétase
  • ornitinémie
  • citrullinémie
  • acidurie argininosuccinique
  • cystinosis
  • homocystinuria (déficit en cystathionine beta-synthase)

- histidine
- beta-amino acids
- lysine
- aspartic acid

  • aspartylglucosaminurie

II. inherited disorders of lipid metabolism

A. Anomalies of fatty acid beta oxidation

B. Anomalies of very long chain fatty acids (peroxysomal diseases)

- Group 1. Anbormal peroxysomes (multiple enzymatic deficiency)

  • Zellweger disease
  • neonatal adrenoleukodystrophy
  • infantile REfsum disease
  • pipecolic acidemia

- Group 2. Normal peroxysome. Isolated enzymatic deficiency

  • X-linked adrenoleucodystrophy
  • acatalasemia
  • hyperoxaluria type 1
  • 3-oxoacyl-CoA thiolase deficiency (syndrome de pseudo-Zellweger)
  • acyl-CoA oxidase deficiency
  • bi-fonctionnal enzyme deficiency
  • dihydroxy-acetone-phosphate acetyl-transférase deficiency

— c. Groupe 3. Present peroxysomes but abnormal structure. Multiple enzymatic deficiencies

  • punctate rhizomelic chondrodysplasia
  • Zellweger-like syndrome

C. Lipid lysosomal storage diseases (lipidoses)

- sphingolipidosis

  • ceramidosis
    • glycosylceramide lipidosis ( Gaucher disease)
    • ceramidase (Farber disease ou Farber lipogranulomatosis)
  • glycosphingolipidosis
    • Fabry disease
    • gangliosidosis type I (GM1)
    • gangliosidosis type II (GM2)
      • type I (Tay-Sachs disease)
      • type II (Sandhoff disease)
  • phosphosphingolipidosis
    • sphingomyeline-cholesterol lipidosis (Niemann-Pick disease) (MIM.257200)
      • Niemann-Pick type A disease (MIM.257200)
      • Niemann-Pick type B disease (MIM.257200)
      • Niemann-Pick type C disease (MIM.257220)
        • Niemann-Pick type C1 disease (MIM.257220)
        • Niemann-Pick type C2 disease - deficiency of HE1 (human epididymis-1) (MIM.601015)
      • Niemann-Pick type D disease
      • Niemann-Pick type E disease (MIM.257200)
  • alpha-N-acétylgalactosaminidase disease (Schindler disease)
  • metachromatic leucodystrophy (sulphatide lipidosis)
  • sulfatase mutiple deficiency
  • Krabbe disease
  • Batten disease
  • Wolman disease (lysosomal lipase acide deficiency)
  • cholestérol esters storage disease
  • fucosidosis

D. Anomalies of lipoproteins transport and metabolism

- 1. familial hypercholestérolemia

  • heterozygous familial hypercholestérolemia
  • homozygous familial hypercholestérolemia

- 2. apo B-100 familial deficiency
- 3. combined familial hyperlipidemia
- 4. familial hyperapobetalipoproteinemia
- 5. elevated Lp(a)
- 6. familial dysbetalipoproteinemia
- 7. sitosterolemia (phytosterolemia)
- 8. familial hypertriglyceridemia (FHTG)
- 9. hyperchylomicronemia

  • lipoprotéine lipase deficiency (LPL)
  • apoC-II deficiency (LPL cofactor)
  • type 5 familial hyperlipoproteinemia

- 10. HDL deficiency

  • HDL familial deficiency (High Density Lipoprotein) (Tangier disease)
  • lecithine-cholesterol acyltransferase deficiency (LCAT)

- 11. abetalipoproteinemia et hypobetalipoproteinemia
- 12. cerebrotendinous xanthomatosis
- 13. other lipidic anomalies

  • familial hepatosteatosis
  • congenital total lipodystrophy

III. Defects in metabolism of carbohydrates

Intestinal defects of carbohydrate metabolism
Defetcs in intermediary carbohydrate metabolism
- Defetcs without lactic acidosis or abnormal glycogen storage
— Anomalies du métabolisme du galactose
— Anomalies du métabolisme du fructose
- Anomalies du métabolisme intermédiaire des glucides avec acidose lactique
- Maladie du stockage du glycogène (Glycogénoses)
- GSD Ia
- GSD Ib
- GSD Ic
- GSD IIa et IIb
- GSD IV - Amylopectinosis
- GSD IX a,b,c

F. Déficit en Xylulose déshydrogénase
G. Déficit en alpha-mannosidase acide (Mannosidose)
- déficit en alpha-fucosidase acide (Fucosidose)
H. Maladie de Lafora

IV. Anomalies du métabolisme des mucopolysaccharides
(Mucopolysaccharidosis ou glycprotéinoses)

A. Maladie de Hurler (Mucopolysaccharidosis IH)
B. Maladie de Scheie (Mucopolysaccharidosis IS)
C. Maladie de Hurler-Scheie (Mucopolysaccharidosis IH-IS)
D. Maladie de Hunter (Mucopolysaccharidosis II)
- type A
- type B
E. Maladie de Sanfilippo (Mucopolysaccharidosis III) (types A, B, C, D)
F. Maladie de Morquio (Mucopolysaccharidosis IV) (types A, B)
G. Kératane et Héparane sulfaturie (Mucopolysaccharidosis VIII)
H. Maladie de Maroteaux-Lamy (Mucopolysaccharidosis VI) (mild and severe type)
I. Beta-glucuronidase deficiency (Mucopolysaccharidosis VI, Sly’s syndrome)
V. Anomalies du métabolisme des mucolipides (Mucolipidosis)
- Mucoplipidosis type I (ML-1) ou lipomucopolysaccharidose ou sialidose de type 2 infantile
- Mucoplipidosis type II (ML-2) (Leroy I-cell syndrome)
- Mucoplipidosis type III (ML-3) (Pseudo-Hurler polydystrophy syndrome)
- Mucoplipidosis type IV (ML-4)

VI. Anomalies of purines and pyrimidines metabolism

- Gout
- Lesh-Nyhan disease
- Hypouricémie
- Xanthinurie
- Déficit en adénosine déaminase
- Déficit en nucléoside phosphorylase
- Déficit en adénine phosphoribosyltransférase
- Acidurie orotique

VII. Anomalies du métabolisme des porphyrines (heme metabolism) (Porphyrias)
Hepatic porphyrias
- porphyrie aigue intermittente
- porphyrie cutanée tardive
Erythropoietic porphyrias
- protoporphyrie érythropoiétique

VIII. Anomalies du métabolisme des métaux
- cuivre
— Maladie de Wilson
- fer
— Hémochromatose constitutionnelle

IX. Anomalies of oxidative phosphorylation (OXPHOS)
- Defects in structural OXPHOS genes
- Faulty intergenomic communication
- OXPHOS assembly, homeostasis and import defects
- Mitochondrial cytopathy

IX. Anomalies vitaminiques

X. Anomalies des folates

- déficit en 5,10-@Methylenetetrahydrofolate reductase (MTHFR) (omim)

See also

- diseases / Diseases

  • storage diseases


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- Abramovich CM, Prayson RA, McMahon JT, Cohen BH. Ultrastructural examination of the axillary skin biopsy in the diagnosis of metabolic diseases. Hum Pathol. 2001 Jun;32(6):649-55. PMID: 11431721

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- SIMD, Society of Inherited Metabolic Disorders