A 9-year-old boy evaluated for progressive spastic diplegia has mild intellectual disability, normal early development, and only modest hyperammonemia. Plasma arginine is grossly elevated and urine orotic acid is normal. The most likely diagnosis is:

• A Citrullinemia type I
• B OTC deficiency
• C Arginase deficiency (argininemia) ✓
• D Homocitrullinuria due to ORNT1 defect

Explanation

Arginase deficiency uniquely among urea cycle disorders presents with progressive spasticity rather than severe neonatal hyperammonemia, and it shows marked hyperargininemia. Because the block sits at the last step, upstream intermediates like citrulline stay near normal and orotic acid is not elevated, unlike OTC deficiency. Treatment combines arginine restriction with supplementation of essential amino acids other than arginine precursors.

Reference: Nelson Textbook of Pediatrics, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.