Metabolic & Storage Diseases
What You'll Learn
Sphingolipidoses Overview Table
| Disease |
Enzyme Deficiency |
Accumulated Substrate |
Key Features |
| Tay-Sachs | Hexosaminidase A | GM2 ganglioside | Cherry-red spot, progressive neurodegeneration, NO hepatosplenomegaly; Ashkenazi Jewish |
| Sandhoff | Hexosaminidase A + B | GM2 ganglioside + globoside | HEXB gene; deficiency of both Hex A (αβ) and Hex B (ββ) isoenzymes (beta-subunit defect); GM2 + globoside + GA2 accumulation; visceral involvement distinguishes from Tay-Sachs |
| Niemann-Pick A | Sphingomyelinase (acid) | Sphingomyelin | Cherry-red spot, foam cells, hepatosplenomegaly, fatal by age 3 |
| Niemann-Pick B | Sphingomyelinase (acid) | Sphingomyelin | Hepatosplenomegaly, pulmonary disease, NO neurologic involvement |
| Niemann-Pick C | NPC1/NPC2 (cholesterol transporter) | Unesterified cholesterol | Vertical supranuclear gaze palsy, ataxia, dystonia, dementia, cataplexy (often triggered by laughter — gelastic-triggered) |
| Gaucher (type 1) | Glucocerebrosidase (GBA) | Glucocerebroside | Most common LSD; hepatosplenomegaly, bone disease; NO neuro involvement |
| Gaucher (type 2/3) | Glucocerebrosidase (GBA) | Glucocerebroside | Neuronopathic forms; type 2 = acute infantile (fatal); type 3 = chronic |
| Fabry | Alpha-galactosidase A | Globotriaosylceramide (Gb3) | X-linked recessive; acroparesthesias, angiokeratomas, corneal verticillata, renal failure, stroke |
| GM1 gangliosidosis | Beta-galactosidase | GM1 ganglioside | Cherry-red spot, skeletal dysplasia, hepatosplenomegaly |
| Krabbe | Galactocerebrosidase | Galactocerebroside | Globoid cell leukodystrophy, irritability, spasticity, peripheral neuropathy |
| Metachromatic leukodystrophy | Arylsulfatase A | Sulfatide | Demyelination (central + peripheral), metachromatic granules on biopsy |
Gaucher Disease Types
| Type |
Onset |
Neurologic? |
Features |
| Type 1 (90%) | Variable | No | Hepatosplenomegaly, pancytopenia, bone crises, Erlenmeyer flask deformity; Ashkenazi Jewish; ERT available |
| Type 2 | Infancy | Yes (acute) | Rapidly progressive; bulbar signs, seizures, spasticity; fatal by age 2 |
| Type 3 | Childhood | Yes (chronic) | Slower neurodegeneration; horizontal supranuclear gaze palsy, myoclonus, ataxia |
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