A child with spasticity and episodic lethargy has hyperammonemia, marked hyperornithinemia, and urinary excretion of homocitrulline. Which defect best explains these findings?

• A Argininosuccinate lyase deficiency
• B Mitochondrial ornithine-citrulline antiporter (ORNT1, SLC25A15) deficiency ✓
• C Glycine cleavage enzyme deficiency
• D Cytosolic fumarase deficiency

Explanation

Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome arises from defective ORNT1, the transporter that imports ornithine into mitochondria in exchange for citrulline. Mitochondrial ornithine depletion stalls OTC, so carbamoyl phosphate spills into the cytosol and feeds the pyrimidine pathway, producing homocitrulline. Elevated citrulline would be expected in argininosuccinate lyase deficiency, whereas here ornithine itself is markedly raised, distinguishing the two.

Reference: Nelson Textbook of Pediatrics, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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