N-Acetylglutamate synthase deficiency
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|N-Acetylglutamate synthase deficiency|
|Other names||Synthetase deficiency|
Signs and symptoms
The symptoms are visible within the first week of life and if not detected and diagnosed correctly immediately consequences are fatal.
The chromosome found to be carrying the gene encoding for N-Acetyl Glutamate synthetase is chromosome 17q (q stands for longer arm of the chromosome) in humans and chromosome 11 in mice. In both organisms, the chromosome consists of seven exons and six introns and non-coding sequence.
Carbamoyl Phosphate Synthase 1, abbreviated as CPS1, is activated by its natural activator N-Acetyl glutamate, which in turn is synthesized from acetyl-CoA and glutamic acid in the reaction catalyzed by N-Acetyl glutamate synthase, commonly called NAGS. N-Acetyl Glutamate is required for the Urea cycle to take place.
Deficiency in N-Acetylglutamate synthase or a genetic mutation in the gene coding for the enzyme, will lead to urea cycle failure in which ammonia is not converted to urea, but rather accumulated in blood leading to the condition called Type I Hyperammonemia. This is a severe neonatal disorder with fatal consequences, if not detected immediately upon birth.
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Although there is currently no cure, treatment includes injections of structurally similar compound, Carglumic acid, an analogue of N-Acetyl Glutamate. This analogue likewise activates CPS1. This treatment mitigates the intensity of the disorder.
Also: hemodialysis for emergent hyperammonemic crisis, Na benzoate, Na phenylacetate, Na phenylbutyrate, low-protein diet supplemented with essential amino acid mixture and arginine, citrulline, experimental attempts at gene therapy, liver transplantation (which is curative), and also N-carbamylglutamate supplementation.
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- Caldovic L, Morizono H, Panglao M, Cheng S, Packman S, Tuchman M (2003). "Null mutations in the N-acetylglutamate synthase gene associated with acute neonatal disease and hyperammonemia". Hum Genet. 112 (4): 364–8. doi:10.1007/s00439-003-0909-5. PMID 12594532. S2CID 27479847.