Hexosaminidase A deficiency causes –
**Core Concept**
Hexosaminidase A (Hex-A) is a lysosomal enzyme crucial for the breakdown of gangliosides, specifically GM2. Its deficiency leads to the accumulation of GM2 ganglioside within neurons, resulting in Tay-Sachs disease.
**Why the Correct Answer is Right**
Hex-A deficiency arises due to mutations in the HEXA gene, which encodes the alpha subunit of the enzyme. The absence or dysfunction of Hex-A leads to the inability to degrade GM2 ganglioside, causing its accumulation within lysosomes. This accumulation triggers cellular damage and ultimately leads to neuronal death. The disease predominantly affects Ashkenazi Jews, with a carrier frequency of approximately 1 in 30.
**Why Each Wrong Option is Incorrect**
**Option A:** Gaucher's disease is caused by glucocerebrosidase deficiency, not hexosaminidase A deficiency.
**Option B:** Fabry's disease is caused by alpha-Gal A deficiency, which leads to the accumulation of globotriaosylceramide.
**Option C:** Niemann-Pick disease is caused by sphingomyelinase deficiency, resulting in sphingomyelin accumulation.
**Clinical Pearl / High-Yield Fact**
Tay-Sachs disease is an autosomal recessive disorder, meaning that both parents must be carriers of the mutated gene for their offspring to develop the disease.
**Correct Answer: C. Niemann-Pick disease is caused by sphingomyelinase deficiency, resulting in sphingomyelin accumulation.**