A 10-month-old infant presents with developmental regression, exaggerated startle response, cherry-red spot on fundoscopy, and progressive hypotonia. Enzyme assay shows absent hexosaminidase A activity. Which metabolic pathway is disrupted?
- A Sphingomyelin degradation
- B GM2 ganglioside degradation ✓
- C Glucocerebroside degradation
- D Galactocerebroside degradation
Correct answer: B. GM2 ganglioside degradation
Explanation
Absent hexosaminidase A activity is diagnostic of Tay-Sachs disease (GM2 gangliosidosis type 1), in which GM2 ganglioside accumulates in neurons due to deficiency of beta-hexosaminidase A (HEXA gene, chromosome 15). Clinical features include early-onset neurodegeneration, exaggerated Moro/startle, cherry-red spot, and progressive motor and cognitive regression. Niemann-Pick involves sphingomyelin, Gaucher involves glucocerebroside, and Krabbe involves galactocerebroside.
Reference: Ghai Essential Pediatrics, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.