N-carbamylglutamate enhances ammonia detoxification in a patient with decompensated methylmalonic aciduria

• Published in: Molecular genetics and metabolism Vol. 79; no. 4; pp. 303 - 304
• Main Authors: Gebhardt, Boris, Vlaho, Stefan, Fischer, Doris, Sewell, Adrian, Böhles, Hansjosef
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-08-2003
• Subjects: Amino Acid Metabolism, Inborn Errors - drug therapy; Carbamyglutamate; Glutamates - administration & dosage; Glutamates - pharmacokinetics; Glutamates - therapeutic use; Humans; Hyperammonaemia; Hyperammonemia - drug therapy; Hyperammonemia - etiology; Inactivation, Metabolic; Male; Methylmalonic Acid - urine; Methylmalonic aciduria (MMA); Carbamyglutamate; Hyperammonaemia; Methylmalonic aciduria (MMA)
• ISSN: 1096-7192; 1096-7206
• DOI: 10.1016/S1096-7192(03)00095-7

In patients with methylmalonic aciduria (MMA), the accumulating metabolite propiony-CoA results in an inhibition of the urea circle via the decreased synthesis of
N-acetylglutamate, an essential activator of carbamylphosphat synthetase (CPS). This results in one of the major clinical problems which is hyperammonaemia. In a patient with decompensated MMA, the CPS activator carbamylglutamate was tested for its ability to antagonize the propionyl-CoA-induced hyperammonaemia. Oral carbamylgutamate administration resulted in an impressive increase in ammonia detoxification compared to peritoneal dialysis. Safe, fast and easy to administer, carbamylglutamate improves the acute therapy of decompensated MMA by increasing ammonia detoxification and avoiding hyperammonaemia.