A 6-month-old infant is brought with progressive loss of motor milestones, exaggerated startle response to sound, cherry-red spot on fundoscopy, and no hepatosplenomegaly. Enzyme assay shows deficiency of hexosaminidase A. Which statement about the storage material in this condition is CORRECT?
- A GM1 ganglioside accumulates due to deficiency of beta-galactosidase
- B Glucocerebrosides accumulate in macrophages of the liver and spleen causing hepatosplenomegaly
- C Sphingomyelin accumulates in the reticuloendothelial system causing the cherry-red spot
- D GM2 ganglioside accumulates due to hexosaminidase A deficiency in neurons ✓
Explanation
Tay-Sachs disease is caused by hexosaminidase A deficiency, leading to accumulation of GM2 ganglioside specifically in neurons. The clinical triad is progressive neurological deterioration, exaggerated startle response, and cherry-red spot (due to contrast of lipid-laden retinal ganglion cells surrounding the fovea vs. the normal fovea). Crucially, there is NO hepatosplenomegaly (differentiating it from Niemann-Pick disease, where sphingomyelin accumulates in the RES). GM1 gangliosidosis involves beta-galactosidase deficiency. Gaucher disease involves glucocerebroside accumulation with hepatosplenomegaly.
Reference: Ghai Essential Pediatrics, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.