title: N-carbamylglutamate protects patients with decompensated propionic aciduria from hyperammonaemia.
abstract: In patients with propionic aciduria, the accumulating metabolite propionyl-CoA causes a disturbance of the urea cycle via the inhibition of N-acetylglutamate synthesis. Lack of this allosteric activator results in an inhibition of carbamoylphosphate synthase (CPS). This finally leads to hyperammonaemia. In two patients with decompensated propionic aciduria the CPS activator carbamylglutamate was tested for its ability to antagonize the propionyl-CoA associated hyperammonaemia. Oral carbamyl glutamate administration resulted in a significant increase in ammonia detoxification and could avoid further dialysis therapy. Safe, fast and easy to administer, carbamyl glutamate improves the acute therapy of decompensated propionic aciduria by increasing ammonia detoxification and avoiding hyperammonaemia.
authors.affiliation: Department of General Paediatrics, Johann Wolfgang Goethe University of Frankfurt a.M., Theodor Stern Kai 7, D-60590 Frankfurt, Germany. Boris-Rainer.Gebhardt@kgu.de
authors.forename: B
authors.initials: B
authors.lastname: Gebhardt
authors.forename: S
authors.initials: S
authors.lastname: Dittrich
authors.forename: S
authors.initials: S
authors.lastname: Parbel
authors.forename: S
authors.initials: S
authors.lastname: Vlaho
authors.forename: O
authors.initials: O
authors.lastname: Matsika
authors.forename: H
authors.initials: H
authors.lastname: Bohles
mesh_terms: D005971:Glutamates / Q000008:administration & dosage*; D006801:Humans; D022124:Hyperammonemia / Q000188:drug therapy* / Q000209:etiology / Q000652:urine*; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000188:drug therapy / Q000652:urine; D008297:Male; D008661:Metabolism, Inborn Errors / Q000188:drug therapy* / Q000652:urine*; D011422:Propionates / Q000652:urine*; D012720:Severity of Illness Index
chemical_list: D005971:Glutamates; D011422:Propionates; C006895:N-carbamylglutamate; C029658:propionic acid