N‐acetylglutamate synthase deficiency and the treatment of hyperammonemic encephalopathy

Publisher Website
Google Scholar
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.