Gaucher disease involves accumulation of glucocerebrosides in macrophages of the spleen, liver, and bone marrow. The enzyme deficient in Gaucher disease is:

• A Sphingomyelinase — deficient in Niemann-Pick disease, not Gaucher
• B Hexosaminidase A — deficient in Tay-Sachs disease, causing GM2 gangliosidosis
• C Alpha-galactosidase A — deficient in Fabry disease, causing globotriaosylceramide accumulation
• D Glucocerebrosidase (acid beta-glucosidase, GBA gene) — cleaves glucose from glucocerebroside; its deficiency causes glucocerebroside accumulation in macrophages ✓

Explanation

Gaucher disease is the most common lysosomal storage disorder, caused by autosomal recessive deficiency of glucocerebrosidase (acid beta-glucosidase, encoded by the GBA gene). This enzyme cleaves the glucose moiety from glucocerebroside (glucosylceramide) in lysosomes. Macrophages (especially in spleen, liver, bone marrow) that phagocytose old erythrocytes accumulate glucocerebroside as a wrinkled tissue paper-like cytoplasm (Gaucher cells). Treatment is enzyme replacement therapy (imiglucerase). Gaucher type I is non-neuropathic; types II and III involve neurological involvement.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.