Which enzyme is deficient in Gaucher disease, the most common lysosomal storage disorder?

Explanation

## Gaucher Disease — Enzyme Deficiency **Key Point:** Gaucher disease results from deficiency of **glucocerebrosidase** (also called β-glucosidase or acid β-glucosidase), a lysosomal enzyme that catalyzes the hydrolysis of glucocerebroside (glucosylceramide) to glucose and ceramide. ### Pathophysiology Without functional glucocerebrosidase, glucocerebroside accumulates within lysosomes of macrophages, creating characteristic **Gaucher cells** — lipid-laden macrophages with a "wrinkled tissue paper" or "crumpled silk" appearance on light microscopy. ### Epidemiology & Significance - **Most common lysosomal storage disorder** worldwide - Autosomal recessive inheritance - Three clinical types: Type 1 (non-neuropathic, most common), Type 2 (acute neuropathic, infantile), Type 3 (chronic neuropathic, juvenile) - Type 1 is most prevalent in Ashkenazi Jewish populations ### Clinical Features - Hepatosplenomegaly (often massive) - Bone involvement: pain, pathological fractures, avascular necrosis - Anemia and thrombocytopenia (from bone marrow infiltration) - Growth retardation in childhood forms **High-Yield:** Glucocerebrosidase deficiency → glucocerebroside accumulation → Gaucher cells → hepatosplenomegaly and bone disease. [cite:Robbins 10e Ch 5]