A 6-month-old infant presents with progressive psychomotor regression, exaggerated startle response to noise, a cherry-red spot on fundoscopy, and macrocephaly. Enzyme assay shows absent hexosaminidase A activity. Which of the following is the most accurate statement about the molecular basis of Tay-Sachs disease?
- A Deficiency of hexosaminidase A causes accumulation of GM1 ganglioside
- B Deficiency of hexosaminidase A (alpha subunit HEXA mutation) leads to GM2 ganglioside accumulation in lysosomes ✓
- C The disease is caused by deficiency of both hexosaminidase A and B, both encoded on HEXB gene
- D Cherry-red spot in Tay-Sachs results from retinal ganglion cell hyperplasia
Explanation
Tay-Sachs disease results from mutations in HEXA gene encoding the alpha subunit of hexosaminidase A (HexA is a heterodimer of alpha and beta subunits). Absent HexA activity leads to accumulation of GM2 ganglioside in lysosomes of neurons throughout the brain and retina. Sandhoff disease results from HEXB gene mutation (lacking both HexA and HexB). GM1 gangliosidosis is caused by beta-galactosidase deficiency. The cherry-red spot in Tay-Sachs occurs because the perifoveal ganglion cells (which are swollen with lipid) appear whitish-gray, making the fovea (which has no ganglion cells and shows the underlying choroidal redness) appear red by contrast — it is not due to hyperplasia.
Reference: Ghai Essential Pediatrics, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.