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Valproate-induced worsening of seizures: clue to underlying diagnosis

Radhika Dhamija1, Ralitza H Gavrilova, Elaine C Wirrell

  • 1Department of Pediatric Neurology, Mayo Clinic, Rochester, MN 55905, USA.

Journal of Child Neurology
|April 2, 2011
PubMed

Insights

Valproate sodium can worsen seizures in children with undiagnosed metabolic disorders like nonketotic hyperglycinemia. This antiepileptic drug interferes with glycine metabolism, increasing seizure frequency and severity.

Area of Science:

  • Biochemistry
  • Pediatric Neurology
  • Metabolic Disorders

Background:

  • Valproate sodium is an antiepileptic drug with known risks of hepatotoxicity and encephalopathy in children with undiagnosed metabolic conditions.
  • Metabolic disorders can present with nonspecific symptoms such as developmental delay, failure to thrive, and seizures, complicating diagnosis.

Observation:

  • A 2.5-year-old girl with a history of developmental delay, failure to thrive, and seizures experienced seizure worsening after valproate sodium introduction.
  • This clinical presentation prompted an investigation into an underlying metabolic disorder.

Findings:

  • Extensive investigations led to the diagnosis of nonketotic hyperglycinemia in the patient.
  • Valproate sodium was identified as a contributing factor to the worsening of her metabolic condition and seizure frequency.

Implications:

  • Valproate sodium interferes with glycine cleavage enzyme synthesis in mitochondria, leading to elevated glycine levels.
  • Elevated glycine levels exacerbate underlying metabolic disorders and increase seizure frequency, highlighting the importance of considering metabolic screening before prescribing valproate sodium.

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