THEME AND FOCUS: AMINO ACIDS Case Study: A female neonate did well until approximately 24 hours of age when she became lethargic. A sepsis workup proved negative. At 54 hours, she staed showing focal seizure activity. The plasma ammonia level was found to be 1,000 mmol/L (normal 5-35 mmol/L). Quantitative plasma amino acid levels revealed a marked elevation of argininosuccinate. Lead Question: Which one of the following enzymic activities is most likely to be deficient in this patient?

**Core Concept**
The patient's symptoms, including lethargy, focal seizure activity, and significantly elevated plasma ammonia levels, suggest a disorder of amino acid metabolism. The marked elevation of argininosuccinate in the plasma amino acid levels is a key clue, pointing towards a deficiency in an enzyme involved in the urea cycle.

**Why the Correct Answer is Right**
The urea cycle is a critical metabolic pathway that removes excess nitrogen from the body by converting it into urea. The enzyme argininosuccinate lyase is responsible for converting argininosuccinate into arginine and fumarate in this cycle. A deficiency in argininosuccinate lyase leads to the accumulation of argininosuccinate, which is toxic to the nervous system. This can cause symptoms such as lethargy, seizures, and elevated plasma ammonia levels. The elevated ammonia levels are particularly concerning, as they can cause neurological damage.

**Why Each Wrong Option is Incorrect**
**Option A:** Arginase is an enzyme involved in the urea cycle, but it catalyzes the conversion of arginine to urea and ornithine. A deficiency in arginase would not lead to the accumulation of argininosuccinate.
**Option B:** Ornithine transcarbamylase (OTC) is another enzyme in the urea cycle, but it catalyzes the conversion of ornithine and carbamoyl phosphate to citrulline. A deficiency in OTC would lead to the accumulation of carbamoyl phosphate, not argininosuccinate.
**Option C:** N-Acetylglutamate synthase is an enzyme involved in the regulation of the urea cycle, but it is not directly involved in the conversion of argininosuccinate.

**Clinical Pearl / High-Yield Fact**
A deficiency in argininosuccinate lyase is a classic example of an inborn error of metabolism, and it can be treated with a low-protein diet and supplements of arginine and citrulline.

**Correct Answer:** C.

✓ Correct Answer: B. Argininosuccinate lyase.