Which autosomal recessive disorder is characterized by accumulation of GM2 ganglioside leading to progressive neurodegeneration?

• A. PKU
• B. Tay-Sachs disease
• C. Fragile X syndrome
• D. Lactose tolerance

Answer: (B)

A lysosomal storage disorder where neurons accumulate GM2 ganglioside because the enzyme hexosaminidase A is deficient. This buildup damages brain cells and causes progressive neurodegeneration, which is Tay-Sachs disease. It’s inherited in an autosomal recessive pattern, so two mutated copies are needed for the disorder to appear; carriers are typically healthy. Clinically, infants often seem fine at birth but then develop developmental delays, hypotonia, seizures, vision loss, and usually die in early childhood. A classic finding is the cherry-red spot in the retina.

The other options don’t fit: phenylketonuria involves buildup of phenylalanine due to phenylalanine hydroxylase deficiency, not GM2; Fragile X is an X-linked condition caused by FMR1 repeats and has features like intellectual disability and distinctive facial traits rather than GM2 storage; lactose tolerance refers to a normal variation in lactase enzyme activity, not a neurodegenerative storage disorder.