A newborn with urea cycle defect presents with hyperammonemia on day 2. Plasma citrulline is markedly elevated, but argininosuccinate is absent. Argininosuccinic aciduria is ruled out. Which enzyme defect best explains this biochemical pattern?
- A Argininosuccinate synthetase deficiency (Citrullinemia Type I) ✓
- B Ornithine transcarbamylase (OTC) deficiency
- C Argininosuccinate lyase deficiency
- D Carbamoyl phosphate synthetase I (CPS I) deficiency
Correct answer: A. Argininosuccinate synthetase deficiency (Citrullinemia Type I)
Explanation
The urea cycle proceeds: NH3 + CO2 → carbamoyl phosphate → citrulline (in mitochondria) → argininosuccinate (cytoplasm) → arginine + fumarate → urea. Argininosuccinate synthetase (CTLN1) condenses citrulline + aspartate → argininosuccinate. Deficiency causes citrulline accumulation (cannot condense) and absence of argininosuccinate (not yet formed). In OTC deficiency, citrulline is low (cannot be formed) and orotic acid is elevated. In argininosuccinate lyase deficiency, argininosuccinate accumulates. In CPS I deficiency, both citrulline and argininosuccinate are low.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
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Written and medically reviewed by the StethoPrep medical team.