Gaucher disease (type I) presents with hepatosplenomegaly, pancytopenia from bone marrow infiltration, and Erlenmeyer flask deformity. Enzyme replacement therapy uses recombinant glucocerebrosidase. The substrate that accumulates is glucocerebroside, which is enriched in which specific cell type?

• A Macrophages (reticuloendothelial cells/Gaucher cells), where sphingolipid turnover from senescent RBC membranes is highest ✓
• B Hepatocytes, where glucocerebroside from bile salt recycling accumulates
• C Neurons exclusively, causing cerebellar atrophy in type I disease
• D Renal tubular cells, causing Fabry-like nephropathy

Explanation

Glucocerebroside (glucosylceramide) is a major sphingolipid component of erythrocyte membranes. Senescent red blood cells are engulfed and degraded by macrophages of the reticuloendothelial system (liver Kupffer cells, splenic macrophages, bone marrow macrophages). In Gaucher disease, lysosomal glucocerebrosidase (beta-glucosidase) deficiency prevents glucocerebroside hydrolysis in macrophages. Glucocerebroside accumulates within lysosomes, forming the characteristic Gaucher cells—lipid-laden macrophages with wrinkled tissue paper cytoplasm. Type I Gaucher is non-neuronopathic because neurons do not substantially recycle erythrocyte-derived sphingolipids. Types II and III involve CNS accumulation from neuronal membrane turnover. ERT (imiglucerase, velaglucerase, taliglucerase) targets macrophages via mannose receptor on macrophage surfaces.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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