A patient with Gaucher disease type 1 has Gaucher cells on bone marrow biopsy. These cells represent lipid-laden macrophages engorged with glucocerebroside. The enzyme deficient in Gaucher disease is:

• A Hexosaminidase A (beta-N-acetylhexosaminidase, deficient in Tay-Sachs)
• B Sphingomyelinase (acid sphingomyelinase, deficient in Niemann-Pick type A/B)
• C Alpha-galactosidase A (deficient in Fabry disease)
• D Glucocerebrosidase (beta-glucosidase/acid beta-glucosidase, GBA gene) ✓

Explanation

Gaucher disease is caused by deficiency of glucocerebrosidase (acid beta-glucosidase, encoded by GBA), leading to accumulation of glucocerebroside (glucosylceramide) in macrophage lysosomes throughout the reticuloendothelial system (bone marrow, spleen, liver). The characteristic 'Gaucher cell' has a crumpled tissue-paper or wrinkled silk cytoplasm appearance on PAS staining, reflecting crystalline glucocerebroside inclusions. Type 1 is non-neuronopathic and amenable to enzyme replacement therapy (imiglucerase). Hexosaminidase A deficiency causes Tay-Sachs (GM2 gangliosidosis). Sphingomyelinase deficiency causes Niemann-Pick A/B. Alpha-galactosidase A deficiency causes Fabry disease.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.