A 3-year-old child is brought with regression of milestones, hyperacusis, a 'cherry-red spot' on fundoscopy, startle response to noise, progressive neurological deterioration, and hepatosplenomegaly is absent. Hexosaminidase A activity is undetectable in leukocytes. What is the inheritance pattern of this condition, and which enzyme/substrate is deficient?
- A Autosomal recessive; hexosaminidase A (beta subunit, HEXA gene); GM2 ganglioside ✓
- B X-linked recessive; alpha-galactosidase A; globotriaosylceramide
- C Autosomal recessive; sphingomyelinase; sphingomyelin
- D Autosomal recessive; glucocerebrosidase; glucocerebroside
Explanation
The clinical description — cherry-red spot, progressive neurodegeneration, hyperacusis, absence of hepatosplenomegaly, and undetectable hexosaminidase A — is classic Tay-Sachs disease. It is caused by deficiency of hexosaminidase A (encoded by the HEXA gene, beta subunit), resulting in accumulation of GM2 ganglioside in neurons. It follows autosomal recessive inheritance with high prevalence in Ashkenazi Jewish, French-Canadian, and Cajun populations. Niemann-Pick disease (sphingomyelinase deficiency) and Gaucher disease (glucocerebrosidase deficiency) both cause hepatosplenomegaly. Fabry disease (alpha-galactosidase A) is X-linked and presents with angiokeratomas and acroparesthesias.
Reference: Ghai Essential Pediatrics, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.