A 3-year-old child presents with progressive hepatosplenomegaly, developmental regression, and a cherry-red spot on fundoscopy. Enzyme assay shows deficient beta-hexosaminidase A AND B activity. Which diagnosis is MOST consistent?

• A Tay-Sachs disease
• B Niemann-Pick disease type A
• C Gaucher disease type 2 (neuronopathic)
• D Sandhoff disease ✓

Explanation

Sandhoff disease is caused by deficiency of BOTH beta-hexosaminidase A and B (due to HEXB gene mutation), leading to accumulation of GM2 gangliosides and globoside in neurons AND visceral organs (hepatosplenomegaly). In contrast, Tay-Sachs disease has deficient hex A only (HEXA mutation) with cherry-red spot but typically WITHOUT hepatosplenomegaly. Niemann-Pick type A shows hepatosplenomegaly and cherry-red spot but involves sphingomyelinase deficiency. Gaucher type 2 involves glucocerebrosidase deficiency with neurodegeneration and organomegaly but no cherry-red spot.

Reference: Ghai Essential Pediatrics, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.