Expansion
Enzyme deficiency causes substrate accumulation within lysosomes
Expansion
| Disease | Enzyme | Accumulates | Key features |
|---|---|---|---|
| Gaucher | Glucocerebrosidase | Glucocerebroside | Commonest; hepatosplenomegaly, bone crises, crumpled tissue paper macrophages |
| Tay-Sachs | Hexosaminidase A | GM2 ganglioside | Cherry red spot, no organomegaly, neurodegeneration |
| Niemann-Pick | Sphingomyelinase | Sphingomyelin | Cherry red spot with hepatosplenomegaly |
| Fabry | Alpha-galactosidase A | Ceramide trihexoside | X-linked; angiokeratomas, neuropathic pain, renal failure |
| Krabbe | Galactocerebrosidase | Galactocerebroside | Optic atrophy, peripheral neuropathy |
| Metachromatic leukodystrophy | Arylsulphatase A | Cerebroside sulphate | Demyelination, ataxia |
| Hurler | Alpha-L-iduronidase | Heparan and dermatan sulphate | Coarse features, corneal clouding |
| Hunter | Iduronate sulphatase | Same | X-linked, no corneal clouding, aggressive behaviour |
Most are autosomal recessive; Fabry and Hunter are X-linked.
Two useful discriminators: cherry red spot occurs in Tay-Sachs and Niemann-Pick, and organomegaly separates them. Hurler and Hunter are distinguished by corneal clouding and inheritance.
Enzyme replacement therapy is available for Gaucher, Fabry, Pompe and some mucopolysaccharidoses.