A 6-month-old infant with progressive neurodegeneration, cherry-red spot, and hepatosplenomegaly has foamy macrophages on bone marrow biopsy. Enzyme assay reveals absent beta-glucocerebrosidase. This enzyme cleaves which bond in glucocerebroside?
- A The ester bond between fatty acid and sphingosine (ceramidase reaction)
- B The phosphodiester bond between phosphocholine and ceramide
- C The beta-glucosidic bond between glucose and ceramide ✓
- D The N-acyl bond of the long-chain fatty acid to sphinganine
Correct answer: C. The beta-glucosidic bond between glucose and ceramide
Explanation
Gaucher disease is caused by glucocerebrosidase (acid beta-glucosidase, GBA1) deficiency. This lysosomal enzyme cleaves the beta-glucosidic bond between glucose and ceramide in glucocerebroside (glucosylceramide), which is the major sphingolipid product of RBC membrane turnover. Accumulation occurs in macrophages/Kupffer cells/Gaucher cells. The description with hepatosplenomegaly without neurological involvement fits Type 1 (non-neuronopathic); cherry-red spot indicates neuronopathic forms (Types 2 and 3).
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.