Table 1 Sphingolipidoses
Disease | Gene | Enzyme/protein deficiency | Accumulated substrate | Main clinical features |
|---|---|---|---|---|
Gaucher disease | GBA | β-Glucocerebrosidase | Glucocerebroside and glucosylsphingosine | Type I (non-neuronopathic): hepatosplenomegaly, thrombocytopenia, bone complications, pulmonary disease. Type II: early onset and short life expectancy, visceral and bone marrow involvement, spasticity, severe neurological manifestations. Type III: visceral and bone marrow involvement, less severe neurological involvement than type II. |
Fabry disease | GLA | α-Galactosidase A | Globotriaosylceramide | Males: cornea verticillata, acroparesthesia, angiokeratomas, gastrointestinal symptoms, hypohidrosis, progressive organ failure (cardiomyopathy, kidney and cerebrovascular disease). Females range from no symptoms to severe manifestations as males. |
Farber disease | ASAH1 | Acid ceramidase | Ceramide | Type I: early onset and premature death, organomegaly, joint contractures, voice hoarseness, neurological manifestations. Type II: intermediate. Type III: mild. Type IV: neonatal-visceral. Type V: neurological-progressive. Type VI: combined Farber and Sandhoff diseases. |
GM1 gangliosidosis | GLB1 | β-Galactosidase | GM1 ganglioside, keratan sulfate and oligosaccharides | Type I: premature death, severe neurological manifestations, organonomegaly, skeletal abnormalities, blindness and deafness. Type II: developmental delay, dementia, cerebellar signs, late loss of vision. Type III: dysarthia, gait disturbances, dystonia, cardiomyopathy. |
GM2 gangliosidosis (Tay–Sachs disease) | HEXA | β-Hexosaminidase α subunit | GM2 ganglioside, glycosphingolipids and oligosaccharides | Weakness, bone abnormalities, neurological manifestations, reduction of consciousness, vision, and hearing. |
GM2 gangliosidosis (Sandhoff disease) | HEXB | β-Hexosaminidase β subunit | GM2 ganglioside, GA2 glycolipid and oligosaccharides | Neurological manifestations, less bone involvement than Tay-Sachs disease. |
GM2 gangliosidosis (GM2 activator deficiency) | GM2A | GM2 ganglioside activator | GM2 ganglioside and glycosphingolipids | Weakness, seizures, loss of vision and hearing, intellectual disability, paralysis. |
Globoid cell leukodystrophy (Krabbe disease) | GALC | Galactosylceramidase | Galactocerebroside and psychosine | Psychomotor dysfunction, seizures, spasticity, cognitive decline. |
Metachromatic leukodystrophy | ARSA and PSAP | Arylsulfatase A and prosaposin | Sulfatides | Unsteady gait, mental regression, seizures, unsteady gait, incontinence, blindness, loss of motor function. Adult form: variable progression. |
Niemann–Pick disease types A and B | SMPD1 | Sphingomyelin phosphodiesterase | Sphingomyelin | Type A: early onset and premature death, lymphadenopathy, organonomegaly, weakness, dysphagia, severe psychomotor dysfunction. Type B: slowly progressive symptoms, no neurodegeneration, variable visceral involvement, organomegaly, liver dysfunction, and lung disease. |