Seizures Due to a KCNQ2 Mutation: Treatment with Vitamin B6

  • Emma S. Reid
  • Hywel Williams
  • Polona Le Quesne Stabej
  • Chela James
  • Louise Ocaka
  • Chiara Bacchelli
  • Emma J. Footitt
  • Stewart Boyd
  • Maureen A. Cleary
  • Philippa B. Mills
  • Peter T. Clayton
Research Report
Part of the JIMD Reports book series (JIMD, volume 27)

Abstract

There is increasing evidence that vitamin B6, given either as pyridoxine or pyridoxal 5′-phosphate, can sometimes result in improved seizure control in idiopathic epilepsy. Whole-exome sequencing was used to identify a de novo mutation (c.629G>A; p.Arg210His) in KCNQ2 in a 7-year-old patient whose neonatal seizures showed a response to pyridoxine and who had a high plasma to CSF pyridoxal 5′-phosphate ratio, usually indicative of an inborn error of vitamin B6 metabolism. This mutation has been described in three other patients with neonatal epileptic encephalopathy. A review of the literature was performed to assess the effectiveness of vitamin B6 treatment in patients with a KCNQ2 channelopathy. Twenty-three patients have been reported to have been trialled with B6; in three of which B6 treatment was used alone or in combination with other antiepileptic drugs to control seizures. The anticonvulsant effect of B6 vitamers may be propagated by multiple mechanisms including direct antagonist action on ion channels, antioxidant action on excess reactive oxygen species generated by increased neuronal firing and replenishing the pool of pyridoxal 5′-phosphate needed for the synthesis of some inhibitory neurotransmitters. Vitamin B6 may be a promising adjunctive treatment for patients with channelopathies and the wider epileptic population. This report also demonstrates that an abnormal plasma to CSF pyridoxal 5′-phosphate ratio may not be exclusive to inborn errors of vitamin B6 metabolism.

Supplementary material

421110_1_En_460_MOESM1_ESM.docx (44 kb)
Data S1: Clinical details of the 23 patients identified who have mutations in KCNQ2 that have been trialled on treatment with pyridoxine or pyridoxal 5′-phosphate. Responses to treatment are stated where available
421110_1_En_460_MOESM2_ESM.docx (16 kb)
Data S2: Plasma amino acid analysis
421110_1_En_460_MOESM3_ESM.docx (18 kb)
Data S3: Whole-exome sequencing and touchdown polymerase chain reaction (PCR) conditions
421110_1_En_460_MOESM4_ESM.docx (14 kb)
Data S4: Plasma PLP reference ranges

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Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Emma S. Reid
    • 1
  • Hywel Williams
    • 1
  • Polona Le Quesne Stabej
    • 1
  • Chela James
    • 1
  • Louise Ocaka
    • 1
  • Chiara Bacchelli
    • 1
  • Emma J. Footitt
    • 2
  • Stewart Boyd
    • 3
  • Maureen A. Cleary
    • 2
  • Philippa B. Mills
    • 1
  • Peter T. Clayton
    • 1
  1. 1.Centre for Translational Omics, Genetics and Genomic MedicineUCL Institute of Child HealthLondonUK
  2. 2.Metabolic Medicine DepartmentGreat Ormond Street Hospital NHS Foundation TrustLondonUK
  3. 3.Electrophysiology DepartmentGreat Ormond Street Hospital NHS Foundation TrustLondonUK

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