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inherited diseases of lipid metabolism

Wednesday 26 May 2004

Alterations in lipid homeostasis are known to severely affect neuronal function and cause neurodegenerative diseases.

Enzymes of the sphingolipid and ganglioside pathways in particular are known to be involved in neurodegenerative disorders.

For example, in Faber disease, ceramide levels are changed and in Niemann-Pick diseases the sphingomyelin (SM) level is drastically increased by a lack of acid sphingomyelinase activity, an SM-degrading enzyme.

Alterations in lipid homeostasis

Diseases Affected lipids Enzymatic defects
Ceremidosis Ceramides -
Faber disease ceramide acid ceramidase
Phosphosphingolipidosis Phosphosphingolipids -
Niemann-Pick Disease sphingomyelin sphingomyelinase
Glycosphingolipidosis Glycosphingolipids -
Krabbe disease galactosylceramide galactosylsphingosine galactosylceramidase
Gaucher disease glucosylceramide glucosylsphingosine glucosylceramidase
Fabry disease digalactosylceramide α-galactosidase A
Tay-Sachs disease GM ganglioside β-hexosaminidase A
Sandhoff disease GM ganglioside β-hexosaminidase A and B
Metachoromatic leukodystrophy sulfatide arylsulfatase A (sulfatidase)
Multiple sulfatase deficiency sulfatide arylsulfatase A, B, C
Sulfatidase-activator deficiency (sap-B deficiency) sulfatide globotriaosylceramide, digalactosylceramide, GM3 ganglioside sulfatidase activator (SAP-1, SAP-B)
SAP-2 deficiency glucosylceramide SAP-2 (SAP-C)
SAP-precursor deficiency all glycolipids with short sugarchains, e.g. Cer, GlcCer, LacCer, GalCer, DigalCer, sulfatide SAP precursor SAP-A, -B, -C, -D
GM1-gangliosidosis GM1 ganglioside GM1 ganglioside, β-galactosidase
GM2-gangliosidosis (B1 variant) GM2 ganglioside β-hexosaminidase A
GM2-gangliosidosis (AB variant) GM2 ganglioside β-hexosaminidase A

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. Peroxysomes présents mais structure anormale. Déficits enzymatiques multiples.

  • Chondrodysplasie ponctuée rhizomélique
  • Syndrome de Zellweger-like

C. Lipid lysosomal storage diseases (lipidoses)

- sphingolipidosis

  • ceramidosis
    • ceramidase (Farber disease ou Farber lipogranulomatosis)
  • phosphosphingolipidosis
    • sphingomyelinosis (sphingomyeline-cholesterol lipidosis or 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)
  • glycosphingolipidoses
    • cerebrosidoses
      • glycocerebrosidosis (Gaucher disease or glycosylceramide lipidosis)
      • galactocerebrosidosis (Krabbe disease)
    • gangliosidosis type I (GM1)
    • gangliosidosis type II (GM2)
      • type I (maladie de Tay-Sachs)
      • type II (maladie de Sandhoff)
  • alpha-N-acétylgalactosaminidase disease (Schindler disease)
  • metachromatic leucodystrophy (sulphatide lipidosis)
  • sulfatase mutiple deficiency
  • glycolipidoses
    • Fabry disease
  • neuronal ceroid lipofuscinoses
    • neuronal ceroid lipofuscinosis-1 (CLN1) (mutation in PPT1 - MIM.600722 encoding palmitoyl-protein thioesterase-1)
    • neuronal ceroid lipofuscinosis-2 (CLN2) (mutation in TPP1 - MIM.607998)
    • neuronal ceroid lipofuscinosis-3 (CLN3) or Batten disease (mutation in CLN3 - MIM.607042)
    • neuronal ceroid lipofuscinosis-4 (CLN4A and CLN4B)
    • neuronal ceroid lipofuscinosis-5 (CLN5) (mutation in CLN5 - MIM.608102)
    • neuronal ceroid lipofuscinosis-6 (CLN6) (mutation in CLN6 - MIM.606725)
    • neuronal ceroid lipofuscinosis-7 (CLN7) (late-infantile) (mutation in MFSD8 - MIM.611124 encoding a putative lysosomal transporter
    • neuronal ceroid lipofuscinosis-8 (CLN8) (mutation in CLN8 - MIM.607837)
    • neuronal ceroid lipofuscinosis-9 (CLN9)
    • neuronal ceroid lipofuscinosis-10 (CLN10) (mutation in CTSD encoding cathepsin D - MIM.116840)
  • Wolman disease (lysosomal lipase acide deficiency)
  • cholestérol esters storage disease
  • fucosidosis