Related Experiment Video
Updated: May 30, 2026

Identification and Classification of Position-specific GABAA Receptor Subunit Missense Variants for Their Role In Hippocampal Pyramidal Neurons
Published on: June 6, 2025
Perioperative exacerbation of valproic acid-associated hyperammonemia: a clinical and genetic analysis
Dmitri Bezinover1, Marek Postula, Kathleen Donahue
1Department 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
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.
Related Concept Videos
Drug Toxicity: Risk factors
Pharmacogenetics of Drug Metabolism: Overview
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Principles of Pharmacogenetics: Types of Genetic Variants
Hepatic Encephalopathy
Antiepileptic Drugs: Glutamate Antagonists
