Lysosomal storage disorders

Lysosomal storage disorders

They are characterized by deficiencies of specific lysosomal enzymes that lead to inhibition of breakdown of the enzyme substrates causing them to accumulate in the lysosomes. All lysosomal storage disorders are AR except Fabry’s disease which is X-linked. Following types are seen:

1. Gaucher’s disease

• Accumulation of glucocerebrosides
• Most common LSD
• Hepatosplenomegaly, osteoporosis, rarely CNS involvement, pancytopenia
• Treat with enzyme replacement therapy
• “Crumpled tissue paper” cytoplasm of macrophages called Gaucher cells

2. Tay Sachs disease

• Accumulation of GM2 gangliosides
• Rapid, progressive, fatal neurodegeneration
• Blindness
• Muscular weakness, seizures
• Cherry red spot on the macula
• Onion skinning of lysosomes
• No hepatosplenomegaly

3. Krabbe Disease (Globoid cell leukodystrophy)

• Accumulation of galactocerebrosides
• Mental and motor retardation
• Blindness, deafness, loss of myelin
• Globoid bodies (glycolipid laden macrophages) seen in the white matter of the brain

4. Metachromatic Leukodystrophy

• Accumulation of sulfatides
• Demyelination, cognitive deterioration, ataxia
• Progressive paralysis, infantile dementia
• Nerves stain yellow-brown with crystal violet

5. Niemann-Pick Disease

• Accumulation of sphingomyelin
• Hepatosplenomegaly
• Type A shows neurodegeneration
• Cherry red macula, lipid laden foam cells

6. Fabry’s Disease

• Accumulation of globosides
• Only X linked LSD.
• Red-purple skin rash, angiokeratomas
• Renal and heart failure
• Burning pain in lower extremities