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

Anesth Analg. 2011 Oct;113(4):858-61. doi: 10.1213/ANE.0b013e318228a001. Epub 2011 Aug 4.

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Carbamoyl-Phosphate Synthase (Ammonia) / deficiency
  • Carbamoyl-Phosphate Synthase (Ammonia) / genetics*
  • Carbamoyl-Phosphate Synthase I Deficiency Disease
  • Chronic Disease
  • DNA Mutational Analysis
  • Device Removal
  • Electric Power Supplies
  • Genetic Predisposition to Disease
  • Heterozygote
  • Humans
  • Hyperammonemia / chemically induced
  • Hyperammonemia / enzymology
  • Hyperammonemia / etiology*
  • Hyperammonemia / genetics
  • Male
  • Mutation, Missense
  • Neurosurgical Procedures / adverse effects*
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Urea Cycle Disorders, Inborn / complications
  • Urea Cycle Disorders, Inborn / genetics*
  • Vagus Nerve Stimulation / instrumentation
  • Valproic Acid / adverse effects*

Substances

  • Valproic Acid
  • Carbamoyl-Phosphate Synthase (Ammonia)