A neonate presents with severe hyperammonemia on day 3 without elevation of any urea cycle intermediate; citrulline, argininosuccinate, and arginine are all low, and urine orotic acid is normal. Enzyme assay shows absent activation of CPS-I. Which drug provides rational therapy?

• A Sodium benzoate alone
• B Allopurinol
• C Carglumic acid, an N-acetylglutamate analogue ✓
• D Sapropterin dihydrochloride

Explanation

This pattern indicates N-acetylglutamate synthetase deficiency: CPS-I lacks its obligatory allosteric activator, so the entire cycle runs idle with low levels of all downstream intermediates and no orotic acid rise. Carglumic acid, N-carbamoyl-L-glutamate, mimics NAG and restores CPS-I activity. Benzoate is adjunctive ammonia scavenging, not curative, and sapropterin targets phenylalanine hydroxylase, a completely separate pathway.

Reference: Nelson Textbook of Pediatrics, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.