A 6-month-old girl develops progressive hepatosplenomegaly, failure to thrive, and type III (neuronopathic) Gaucher disease is suspected. Bone marrow biopsy shows 'crinkled paper' macrophages. Which enzyme is deficient and what is the STORED substrate?
- A Sphingomyelinase — stores sphingomyelin (Niemann-Pick disease)
- B Galactocerebrosidase — stores galactocerebroside (Krabbe disease)
- C Glucocerebrosidase (acid beta-glucosidase) — stores glucocerebroside (glucosylceramide) ✓
- D Arylsulfatase A — stores sulfatide (metachromatic leukodystrophy)
Explanation
Gaucher disease is caused by deficiency of glucocerebrosidase (acid beta-glucosidase, encoded by GBA gene), the lysosomal enzyme that cleaves glucose from glucosylceramide (glucocerebroside). The stored substrate glucosylceramide accumulates in macrophages of liver, spleen, and bone marrow, producing the pathognomonic 'Gaucher cells' — distended macrophages with crinkled tissue paper (wrinkled paper) cytoplasm due to packed glucocerebroside. Type I (non-neuronopathic) is the most common; types II and III involve the nervous system. Enzyme replacement therapy (imiglucerase) is available for type I.
Reference: Ghai Essential Pediatrics, 10th ed.
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