Question

Tay-Sachs disease is due to deficiency of which enzyme?

• A. Hexosaminidase A
• B. Hexosaminidase B
• C. Sphingomyelinase
• D. Alpha-galactosidase

Hint:

GM2 gangliosidosis with a cherry-red spot and no organomegaly.

Answer 1

The Correct Option is A

Step 1: Tay-Sachs disease is a GM2 gangliosidosis, an autosomal recessive lysosomal storage disorder. The missing enzyme is hexosaminidase A, which is needed to degrade the GM2 ganglioside.

Step 2: With hexosaminidase A absent, GM2 ganglioside accumulates in neurons, especially in the brain and retina. This produces progressive neurodegeneration, an exaggerated startle response, hypotonia and the classic cherry-red spot on the macula. There is no hepatosplenomegaly, which helps separate it from Niemann-Pick.

Step 3: The distractors map to other disorders. Sphingomyelinase deficiency causes Niemann-Pick disease, alpha-galactosidase A deficiency causes Fabry disease, and hexosaminidase A plus B deficiency together (deficiency of the beta subunit) causes Sandhoff disease.