• Anesthesia and analgesia · Oct 2011

    Case Reports

    Perioperative exacerbation of valproic acid-associated hyperammonemia: a clinical and genetic analysis.

    • Dmitri Bezinover, Marek Postula, Kathleen Donahue, Brian Bentzen, James McInerney, and Piotr K Janicki.
    • 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
    • Anesth. Analg. 2011 Oct 1; 113 (4): 858-61.

    AbstractWe 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.

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