Аннотация:Abstract Carbamylphosphate synthase is the first enzymatic reaction of the urea cycle. Its activator, N ‐acetylglutamate, is synthesized from acetyl‐CoA and glutamate in a reaction catalyzed by N ‐acetylglutamate synthase (NAGS). We have identified the putative human NAGS gene and report the first mutation in this gene in a family with carbamylglutamate responsive hyperammonemia and normal activity of the urea cycle enzymes. Mutation analysis has a higher diagnostic specificity than the enzymatic assay in NAGS deficiency. A therapeutic trial with carbamylglutamate is recommended whenever hyperammonemia without an organic aciduria, increased orotate excretion, or diagnostic amino acidemia/uria is detected.
