inherited diseases of lipid metabolism
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)
- sphingomyelinosis (sphingomyeline-cholesterol lipidosis or Niemann-Pick disease) (MIM.257200)
- Niemann-Pick type D disease
- Niemann-Pick type E disease (MIM.257200)
- glycosphingolipidoses
- cerebrosidoses
- glycocerebrosidosis (Gaucher disease or glycosylceramide lipidosis)
- galactocerebrosidosis (Krabbe disease)
- cerebrosidoses
- 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
- 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