Urea Cycle Defects and Hyperammonemia

Which enzyme deficiency in the urea cycle results in the accumulation of carbamoyl phosphate and orotic acid, leading to orotic aciduria?

A 3-day-old male neonate born to non-consanguineous parents presents with poor feeding, lethargy, and vomiting. On examination, he is hypotonic with a weak cry. Laboratory investigations reveal: blood ammonia 380 µmol/L (normal <50), pH 7.32, HCO₃⁻ 18 mEq/L, and normal liver function tests. Plasma amino acid analysis shows elevated glutamine and alanine. Urine orotic acid is markedly elevated. Which enzyme deficiency is most likely responsible for this presentation?

A 6-month-old female infant of consanguineous parents presents with recurrent episodes of vomiting, irritability, and developmental delay. During a febrile illness, she develops seizures and altered consciousness. Blood ammonia is 520 µmol/L. Plasma amino acid analysis shows: citrulline 45 µmol/L (normal 20–50), arginine 25 µmol/L (normal 40–130), and elevated glutamine. Urine orotic acid is normal. Urine contains high levels of argininosuccinate. What is the most likely diagnosis?

A 6-year-old girl with a history of recurrent episodes of vomiting, lethargy, and ataxia (triggered by protein-rich meals) is found to have serum ammonia of 180 µmol/L. Plasma amino acid profile shows elevated glutamine, alanine, and **elevated argininosuccinate**. Which is the most appropriate confirmatory investigation?

A 3-year-old boy presents with developmental delay, seizures, and hyperammonemia (plasma ammonia 180 µmol/L). Genetic testing reveals a deficiency in carbamoyl phosphate synthetase I (CPS I). His 6-year-old sister has similar symptoms but normal CPS I activity; genetic testing shows ornithine transcarbamylase (OTC) deficiency. Which clinical feature best distinguishes OTC deficiency from CPS I deficiency?