A 6-month-old infant presents with progressive neurological deterioration, hypotonia, cherry-red spot on fundoscopy, and hepatosplenomegaly. Enzyme assay confirms hexosaminidase A and B deficiency. This is consistent with:

• A Sandhoff disease ✓
• B Tay-Sachs disease
• C Gaucher disease
• D Niemann-Pick disease type A

Explanation

Sandhoff disease results from deficiency of both hexosaminidase A (alpha-beta heterodimer) and hexosaminidase B (beta-beta homodimer) due to mutations in the HEXB gene encoding the beta subunit. Both enzymes are required for GM2 ganglioside degradation; their combined deficiency causes GM2 and GA2 (asialo-GM2) accumulation in neurons and visceral organs, explaining both the neurodegeneration with cherry-red spot and the hepatosplenomegaly. Tay-Sachs (alpha subunit mutation) lacks the beta subunit deficiency and therefore has normal HexB activity with no hepatosplenomegaly.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.