What is the enzymatic defect which causes Hunter’s Disease?
**Core Concept**
Hunter's Disease is a rare, autosomal recessive disorder caused by a deficiency of the enzyme iduronate-2-sulfatase (I2S). This enzyme plays a crucial role in the degradation of glycosaminoglycans (GAGs), specifically dermatan sulfate and heparan sulfate.
**Why the Correct Answer is Right**
The enzymatic defect in Hunter's Disease leads to the accumulation of GAGs in various tissues, including the brain, liver, and bone marrow. This accumulation causes cellular damage, leading to the clinical manifestations of the disease, such as developmental delays, intellectual disability, and progressive neurological deterioration. The deficiency of I2S results in the inability to break down GAGs, leading to their accumulation and subsequent cellular damage.
**Why Each Wrong Option is Incorrect**
**Option A:** This option is incorrect because the enzymatic defect causing Hunter's Disease is not associated with the enzyme alpha-L-iduronidase, which is actually deficient in Hurler's Syndrome.
**Option B:** This option is incorrect because the enzyme glucocerebrosidase is deficient in Gaucher's Disease, not Hunter's Disease.
**Option C:** This option is incorrect because the enzyme arylsulfatase A is deficient in Metachromatic Leukodystrophy, not Hunter's Disease.
**Option D:** This option is incorrect because the enzyme alpha-N-acetylglucosaminidase is deficient in Pompe Disease, not Hunter's Disease.
**Clinical Pearl / High-Yield Fact**
Hunter's Disease is a classic example of a lysosomal storage disorder, where the accumulation of GAGs leads to cellular damage and clinical manifestations. It is essential to remember that each lysosomal storage disorder is caused by a specific enzymatic defect, and understanding these defects is crucial for diagnosis and management.
**Correct Answer:** C. iduronate-2-sulfatase (I2S)