Hyperornithinemia-hyperammonemia- homocitrullinuria {HHH} syndrome is due to deficiency of-
**Core Concept**
Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is a rare, autosomal recessive disorder characterized by elevated levels of ornithine, ammonia, and homocitrulline in the blood and urine. This condition arises due to a defect in the transport of ornithine across the inner mitochondrial membrane.
**Why the Correct Answer is Right**
The correct answer is due to the deficiency of the Ornithine Translocase (OTC) enzyme, which is responsible for the transport of ornithine across the inner mitochondrial membrane. Normally, ornithine is transported into the mitochondria, where it participates in the urea cycle. In HHH syndrome, the impaired transport of ornithine leads to its accumulation in the blood and urine, causing hyperornithinemia and hyperammonemia. The accumulation of ornithine also leads to the formation of homocitrulline through the action of the enzyme peptidase.
**Why Each Wrong Option is Incorrect**
**Option A:** This option is incorrect because the deficiency of the Ornithine Aminotransferase enzyme is associated with gyrate atrophy, a different disorder characterized by progressive vision loss and hyperornithinemia.
**Option B:** This option is incorrect because the deficiency of the Argininosuccinate Synthetase enzyme is associated with citrullinemia type I, a disorder characterized by elevated levels of citrulline and ammonia in the blood and urine.
**Option C:** This option is incorrect because the deficiency of the Argininosuccinase enzyme is associated with citrullinemia type II, a disorder characterized by elevated levels of citrulline and argininosuccinic acid in the blood and urine.
**Option D:** This option is incorrect because the deficiency of the Carbamoyl Phosphate Synthetase I enzyme is associated with carbamoyl phosphate synthetase I deficiency, a disorder characterized by elevated levels of ammonia and orotic acid in the blood and urine.
**Clinical Pearl / High-Yield Fact**
HHH syndrome is a rare but important disorder to recognize, as it can lead to severe hyperammonemia and neurological symptoms if left untreated. Early diagnosis and treatment with ornithine supplementation can help prevent long-term complications.
**Correct Answer:** C. Ornithine Translocase (OTC) enzyme.