title: Perioperative exacerbation of valproic acid-associated hyperammonemia: a clinical and genetic analysis.
abstract: We present a case of significant deterioration of chronic hyperammonemia after general anesthesia for neurosurgery despite aggressive treatment. Preoperative evaluation demonstrated that hyperammonemia was most likely related to valproic acid treatment. Genomic analysis revealed that the patient was heterozygotic for a missense polymorphism in the carbamoyl phosphate synthase 1 gene (4217C>A, rs1047891). This mutation was previously suggested to be associated with chronic hyperammonemia. Replacement of threonine with asparagine decreases the activity of carbamoyl phosphate synthase in the urea cycle. Genetic screening can potentially identify a population at risk before initiation of antiepileptic therapy.
authors.affiliation: Department of Anesthesiology, Penn State College of Medicine, Penn State Milton S. Hershey Medical Center, H187 500 University Dr., PO Box 850, Hershey, PA 17033-0850, USA. dbezinover@hmc.psu.edu
authors.forename: Dmitri
authors.initials: D
authors.lastname: Bezinover
authors.forename: Marek
authors.initials: M
authors.lastname: Postula
authors.forename: Kathleen
authors.initials: K
authors.lastname: Donahue
authors.forename: Brian
authors.initials: B
authors.lastname: Bentzen
authors.forename: James
authors.initials: J
authors.lastname: McInerney
authors.forename: Piotr K
authors.initials: PK
authors.lastname: Janicki
mesh_terms: D000328:Adult; D002222:Carbamoyl-Phosphate Synthase (Ammonia) / Q000172:deficiency / Q000235:genetics*; D020165:Carbamoyl-Phosphate Synthase I Deficiency Disease; D002908:Chronic Disease; D004252:DNA Mutational Analysis; D020878:Device Removal; D011211:Electric Power Supplies; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D022124:Hyperammonemia / Q000139:chemically induced / Q000201:enzymology / Q000209:etiology* / Q000235:genetics; D008297:Male; D020125:Mutation, Missense; D019635:Neurosurgical Procedures / Q000009:adverse effects*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D056806:Urea Cycle Disorders, Inborn / Q000150:complications / Q000235:genetics*; D055536:Vagus Nerve Stimulation / Q000295:instrumentation; D014635:Valproic Acid / Q000009:adverse effects*
chemical_list: D014635:Valproic Acid; D002222:Carbamoyl-Phosphate Synthase (Ammonia)