A patient with Gaucher disease has a bone marrow biopsy showing 'crinkled paper' macrophages. The deficient lysosomal enzyme and its substrate are:

• A Sphingomyelinase; accumulates sphingomyelin
• B Beta-glucocerebrosidase (glucocerebrosidase, GBA); accumulates glucocerebroside (glucosylceramide) ✓
• C Hexosaminidase A; accumulates GM2 ganglioside
• D Alpha-galactosidase A; accumulates globotriaosylceramide (Gb3)

Explanation

Gaucher disease is the most common lysosomal storage disorder, caused by deficiency of acid beta-glucocerebrosidase (glucocerebrosidase, encoded by GBA gene). Glucocerebroside (glucosylceramide) accumulates in macrophage lysosomes, particularly in liver, spleen and bone marrow. The characteristic Gaucher cell has wrinkled/crinkled cytoplasm ('crumpled tissue paper' or 'onion-skin' appearance) from stored glucocerebroside. Treatment: enzyme replacement therapy (imiglucerase). Niemann-Pick disease: sphingomyelinase deficiency → sphingomyelin. Tay-Sachs: hexosaminidase A deficiency → GM2 ganglioside. Fabry disease: alpha-galactosidase A deficiency → Gb3.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.