A neonate develops progressive hyperammonemia, respiratory alkalosis, and encephalopathy. Plasma amino acid analysis shows elevated citrulline and elevated argininosuccinate. The enzyme defect is:

• A Carbamyl phosphate synthetase I (CPS I) deficiency
• B OTC (ornithine transcarbamylase) deficiency
• C Argininosuccinate lyase (ASL) deficiency ✓
• D Arginase deficiency

Explanation

In argininosuccinate lyase (ASL) deficiency, argininosuccinate cannot be cleaved to arginine + fumarate; this causes argininosuccinate to accumulate (detectable in plasma and urine) and citrulline to be elevated (backed up before the block). Hyperammonemia results from urea cycle blockade. CPS I and OTC deficiencies produce low citrulline (the block is before citrulline synthesis). Citrullinemia type I (ASS deficiency) shows massively elevated citrulline but no argininosuccinate. Arginase deficiency shows elevated arginine with spastic diplegia rather than neonatal crisis.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

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Written and medically reviewed by the StethoPrep medical team.