N-carbamylglutamate Augments Ureagenesis and Reduces Ammonia and Glutamine in Propionic Acidemia

OBJECTIVES: The objective of this study was to determine whether N-carbamylglutamate (NCG) reduces plasma levels of ammonia and glutamine and increases the rate of ureagenesis in patients with propionic acidemia (PA). METHODS: Identical 4-hour studies were performed before and immediately after a 3-day trial of oral NCG in 7 patients with PA. An oral bolus of [C-13] sodium acetate was administered at the start of each study, and sequential blood samples were obtained to measure [C-13] urea, ammonia, urea, and amino acids. RESULTS: With longitudinal mixed-effects linear regression, peak [C-13] urea increased after treatment with NCG (from 2.2 to 3.8 mu M; P < .0005). There were concomitant decreases in mean plasma ammonia (59-43 mu M; P < .018) and glutamine (552-331 mu M; P < .0005). CONCLUSIONS: NCG augments ureagenesis and decreases plasma ammonia and glutamine in patients with PA. The drug may serve as an important therapeutic adjunct in the treatment of acute hyperammonemia in this disorder. Pediatrics 2010; 126: e208-e214