Tay-Sachs disease is caused by deficiency of hexosaminidase A (HexA, alpha subunit), while Sandhoff disease is caused by deficiency of both hexosaminidase A and B (beta subunit). Both diseases accumulate GM2 ganglioside. A cherry-red spot at the macula and progressive neurodegeneration are characteristic. How is Tay-Sachs disease distinguished from Sandhoff disease biochemically?
- A Tay-Sachs shows normal HexA and absent HexB on enzyme assay
- B Tay-Sachs accumulates both GM2 ganglioside and glucocerebrosides
- C Sandhoff shows absent HexA but normal HexB, while Tay-Sachs shows absent HexB
- D Tay-Sachs shows absent HexA activity but NORMAL total hexosaminidase (HexB) activity; globoside does NOT accumulate in Tay-Sachs ✓
Explanation
HexA is an alpha-beta heterodimer; HexB is a beta-beta homodimer. In Tay-Sachs (alpha subunit mutation): HexA (alpha-beta) is absent but HexB (beta-beta) is normal or elevated; only GM2 ganglioside accumulates. In Sandhoff (beta subunit mutation): both HexA and HexB are absent; both GM2 ganglioside AND globoside accumulate (globoside is a substrate for HexB but not HexA). This biochemical distinction — globoside accumulation in Sandhoff but not Tay-Sachs — allows enzyme assay-based differentiation. Clinically, both present similarly but Sandhoff tends to have earlier or equivalent onset.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.