N-acetylglutamate synthase deficiency and the treatment of hyperammonemic encephalopathy.
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.
Elpeleg
Orly
O
The Metabolic Disease Unit, Faculty of Medicine, Shaare-Zedek Medical Center, Hebrew University, Jerusalem 91031, Israel. elpeleg@cc.huji.ac.il
Shaag
Avraham
A
Ben-Shalom
Efrat
E
Schmid
Tal
T
Bachmann
Claude
C
D000123:Acetyltransferases / Q000172:deficiency* / Q000235:genetics; D000595:Amino Acid Sequence / Q000235:genetics; D051046:Amino-Acid N-Acetyltransferase; D000818:Animals; D020739:Brain Diseases, Metabolic, Inborn / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D002675:Child, Preschool; D005260:Female; D005971:Glutamates / Q000627:therapeutic use; D006801:Humans; D022124:Hyperammonemia / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D017386:Sequence Homology, Amino Acid
D005971:Glutamates; C006895:N-carbamylglutamate; D000123:Acetyltransferases; D051046:Amino-Acid N-Acetyltransferase; C494874:NAGS protein, human; C494877:Nags protein, mouse