Question

Which disease is caused due to absence of the enzyme hexosaminidase A and results in accumulation of ganglioside \(G_{M2}\) in the brain.

• A. Niemann – Pick disease
• B. Tay – Sachs disease
• C. Von Gierke disease
• D. Cori's disease

Hint:

A classic diagnostic sign of Tay-Sachs disease is a "cherry-red spot" on the macula of the retina, observed during an ophthalmoscopic examination.

Answer 1

The Correct Option is B

Step 1: Understanding the Concept:
Lysosomal storage diseases are genetic disorders characterized by the deficiency of specific lysosomal enzymes.
This deficiency prevents the degradation of target metabolites, causing them to accumulate within lysosomes and disrupt cellular function.

Step 2: Detailed Explanation:
Tay-Sachs disease is an autosomal recessive lysosomal storage disorder caused by mutations in the HEXA gene.
This gene encodes the \(\alpha\)-subunit of the dimeric enzyme \(\beta\)-hexosaminidase A.
Normally, \(\beta\)-hexosaminidase A degrades GM2 gangliosides (glycosphingolipids abundant in neuronal membranes) by cleaving the terminal N-acetylgalactosamine residue.
In the absence of functional hexosaminidase A, GM2 ganglioside accumulates progressively in the lysosomes of neurons.
This accumulation causes lysosomal swelling, cellular toxicity, and cell death, leading to neurodegeneration, developmental regression, blindness, and early childhood mortality.
- Niemann-Pick disease is caused by sphingomyelinase deficiency.
- Von Gierke disease and Cori's disease are glycogen storage diseases affecting carbohydrate metabolism in liver and muscle.

Step 3: Final Answer:
Tay-Sachs disease is caused by the absence of hexosaminidase A, resulting in the accumulation of ganglioside \(G_{M2}\) in the brain.