Lysosomes
On this page 2 sections
Lysosomal Storage Diseases
Lysosomal storage diseases result from defects in lysosomal enzymes, activator proteins or transport mechanisms. Undegraded substrates accumulate in lysosomes and damage tissues.
| Disease | Deficient enzyme | Stored material / classic clue |
|---|---|---|
| Gaucher disease | β-Glucocerebrosidase | Glucocerebroside; hepatosplenomegaly, cytopenias and bone disease |
| Niemann–Pick disease types A/B | Acid sphingomyelinase | Sphingomyelin; hepatosplenomegaly, with neurologic involvement prominent in Type A |
| Tay–Sachs disease | Hexosaminidase A | GM2 ganglioside; neurodegeneration and cherry-red macula |
| Fabry disease | α-Galactosidase A | Glycosphingolipid accumulation; neuropathic pain, angiokeratomas and renal/cardiac disease |
| Pompe disease | Lysosomal acid α-glucosidase | Glycogen; cardiomyopathy and muscle weakness |
| Hurler syndrome | α-L-iduronidase | Glycosaminoglycans; coarse features, corneal clouding and developmental delay |
| Hunter syndrome | Iduronate-2-sulfatase | Glycosaminoglycans; X-linked disorder, typically no corneal clouding |
Important distinctions
Gaucher disease
- Commonly causes hepatosplenomegaly, anemia, thrombocytopenia and bone pain.
- Macrophages containing accumulated lipid may have a characteristic crumpled-tissue-paper appearance.
Tay–Sachs versus Niemann–Pick
| Feature | Tay–Sachs | Niemann–Pick Type A |
|---|---|---|
| Enzyme | Hexosaminidase A | Acid sphingomyelinase |
| Main stored substance | GM2 ganglioside | Sphingomyelin |
| Hepatosplenomegaly | Usually absent | Common |
| Cherry-red macula | May occur | May occur |
| Neurodegeneration | Prominent | Prominent in Type A |
MCQ tip: A cherry-red macula alone does not distinguish Tay–Sachs from Niemann–Pick; look for hepatosplenomegaly and the enzyme defect.