Related Experiment Video

Updated: Mar 30, 2026

How to Obtain Reliable Visual Event-related Potentials in Newborns
07:39

How to Obtain Reliable Visual Event-related Potentials in Newborns

Published on: October 24, 2019

6.9K

Adverse events in a newborn on valproate therapy due to loss-of-function mutations in CYP2C9

Andrea Nagy1, Tamás Bűdi2, Manna Temesvári3

  • 1Heim Pál Children's Hospital, Madarász 22-24, H-1131 Budapest, Hungary.

Epilepsy & Behavior Case Reports
|November 7, 2015
PubMed

Insights

Valproate toxicity risk is higher in young children. Genetic testing for CYP2C9 loss-of-function mutations can prevent severe side effects in pediatric patients.

Area of Science:

  • Pharmacogenomics
  • Pediatric Neurology
  • Clinical Toxicology

Background:

  • Valproate (VPA) is a widely used antiepileptic drug.
  • Increased VPA toxicity risk in young children (<2 years) is known.
  • Age-related pharmacokinetic variations and CYP2C9 metabolism shifts contribute to adverse events.

Purpose of the Study:

  • To report a case of severe valproate-induced toxicity in a premature infant.
  • To investigate the genetic basis for impaired valproate metabolism.
  • To emphasize the importance of CYP2C9 genetic screening in pediatric VPA therapy.

Main Methods:

  • Case report of a premature infant with intraventricular hemorrhage and myoclonic seizures treated with valproate.
  • Clinical monitoring for adverse events including bone marrow depression, hyperammonemia, and elevated alkaline phosphatase.
  • Genetic analysis of the cytochrome P450 2C9 (CYP2C9) gene.

Main Results:

  • The patient developed serious toxic side effects 17 days after initiating valproate.
  • Genetic testing revealed the patient was homozygous for CYP2C9 loss-of-function mutations (CYP2C9*3/*3).
  • This genetic profile led to significantly elevated valproate blood concentrations and toxicity.

Conclusions:

  • Severe valproate toxicity can occur in pediatric patients with specific CYP2C9 genotypes.
  • Impaired valproate metabolism due to CYP2C9 loss-of-function mutations is a key factor.
  • Screening for CYP2C9 inborn errors is crucial for preventing valproate-induced toxicity in children.

Keywords:
Bone marrow depressionCYP2C9 genotypeHyperammonemiaPediatric patientValproate

More Related Videos

Identification and Classification of Position-specific GABAA Receptor Subunit Missense Variants for Their Role In Hippocampal Pyramidal Neurons08:04

Identification and Classification of Position-specific GABAA Receptor Subunit Missense Variants for Their Role In Hippocampal Pyramidal Neurons

Published on: June 6, 2025

1.7K
Author Spotlight: Studying the Impact of Maternal Dietary Deficiencies on Long-Term Offspring Health Outcomes03:19

Author Spotlight: Studying the Impact of Maternal Dietary Deficiencies on Long-Term Offspring Health Outcomes

Published on: June 28, 2024

840

Related Concept Videos

Inborn Errors of Metabolism01:20

Inborn Errors of Metabolism

Phenylketonuria (PKU) is a protein metabolism disorder characterized by high blood levels of the amino acid phenylalanine. This results from a mutation in the gene responsible for phenylalanine hydroxylase, an enzyme that converts phenylalanine into tyrosine. When this enzyme is deficient, phenylalanine builds up in the blood, leading to symptoms such as vomiting, rashes, seizures, growth deficiency, and severe mental retardation. An early diagnosis and a diet restricting phenylalanine intake...
1.0K
Teratogenicity01:07

Teratogenicity

The ability of a drug to produce structural deformations and functional abnormalities in the developing embryo or the fetus is called teratogenicity, and the drug producing this effect is known as a teratogen. Teratogenic effects include stillbirth, miscarriage, intrauterine growth restriction, and neurocognitive delay. A teratogen may affect the embryo at different stages of development, which is important in determining the type and extent of the damage. During blastocyst formation, the early...
4.5K
Pharmacokinetics in Pediatric Patients: Drug Metabolism01:24

Pharmacokinetics in Pediatric Patients: Drug Metabolism

In pediatric care, understanding the nuances of hepatic drug metabolism is crucial, as it significantly differs from that of adults. This divergence is primarily due to the developmental stage of drug-metabolizing enzymes, which affects how medications are processed in the body. In neonates, for instance, the activity of Phase I enzymes—critical for the initial breakdown of drugs—is markedly reduced, functioning at just 20–40% of the levels seen in adults. This reduction poses...
330
Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance01:23

Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance

The elimination half-life and drug clearance of drugs following nonlinear kinetics can vary with dosage. The Michaelis-Menten parameters and drug concentration influence these factors. As the dose increases, the elimination half-life tends to lengthen, resulting in a reduction in clearance and a disproportionately larger area under the curve. The total clearance can be derived from the Michaelis-Menten equation for drugs following a one-compartment model.
A study on guinea pigs examined the...
877
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu01:29

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu

Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
109
Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes01:28

Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes

Cytochrome P450 (CYP450) enzymes are a superfamily of heme-containing monooxygenases that play a pivotal role in Phase I drug metabolism by catalyzing oxidation and reduction reactions.These enzymes transform lipophilic xenobiotics into more hydrophilic metabolites, facilitating subsequent Phase II conjugation and eventual excretion. The CYP450 family is classified into families (e.g., CYP1–CYP3) and subfamilies (e.g., CYP2A, CYP2C), based on amino acid sequence homology.CYP450...
158