- Each is caused by a deficiency in one of the many lysosomal enzymes. Results in an accumulation of abnormal metabolic products.
- Sphingolipidoses
| Tay-Sachs disease
|
Progressive neurodegeneration, developmental delay, “cherry-red” spot on macula (A), lysosomes with onion skin, no hepatosplenomegaly (vs Niemann-Pick). | HeXosaminidase A (“TAy-SaX”) | GM2 ganglioside | AR |
| Fabry disease | Early: Triad of episodic peripheral neuropathy, angiokeratomas (B), hypohidrosis, telangiectasias
Late: progressive renal failure, cardiovascular disease (TIA, stroke, LVH). |
α-galactosidase A | Ceramide trihexoside | XR |
| Metachromatic leukodystrophy | Central and peripheral demyelination with ataxia, dementia. | Arylsulfatase A | Cerebroside sulfate | AR |
| Krabbe disease | Peripheral neuropathy, destruction of oligodendrocytes, developmental delay, optic atrophy, globoid cells. | Galactocerebrosidase | Galactocerebroside, psychosine | AR |
| Gaucher disease | Most common. Hepatosplenomegaly, pancytopenia (pallor, easy bruising, fatigue), osteoporosis, avascular necrosis of femur, bone crises, Gaucher cells (C) (cerebroside & glycolipid-laden macrophages resembling crumpled tissue paper).
|
Glucocerebrosidase (β-glucosidase); treat with recombinant glucocerebrosidase | Glucocerebroside | AR |
| Niemann-Pick disease | Progressive neurodegeneration, hepatosplenomegaly, foam cells (lipid-laden macrophages) (D), “cherry-red” spot on macula (A). | Sphingomyelinase | Sphingomyelin | AR |
- Mucopolysaccharidoses
| Hurler syndrome | Developmental delay, gargoylism, airway obstruction, corneal clouding, hepatosplenomegaly. | α-l-iduronidase | Heparan sulfate, dermatan sulfate | AR |
| Hunter syndrome | Mild Hurler + aggressive behavior, no corneal clouding. | Iduronate-2-sulfatase | Heparan sulfate, dermatan sulfate | XR |
- No man picks (Niemann-Pick) his nose with his sphinger (sphingomyelinase).
- Tay-SaX lacks heXosaminidase.
- Hunters see clearly (no corneal clouding) and aggressively aim for the X (X-linked recessive).
- ↑ incidence of Tay-Sachs, Niemann-Pick, and some forms of Gaucher disease in Ashkenazi Jews.
