Seizures Due to a KCNQ2 Mutation: Treatment with Vitamin B6
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.
We would like to thank the child and her family for participating in this study and for consenting to this report. Additional thanks to Emma Wakeling and Frances Cowen for consenting and referring the patient to our centre, respectively. PBM and PTC are supported by Great Ormond Street Hospital Children’s Charity (GOSHCC). This project was funded by grants from the University College London Impact Award and GOSHCC Metabolic Fund. GOSgene is supported by the NIHR BRC at GOSH for Children NHS Foundation Trust and UCL Institute of Child Health. Views expressed are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health.
- Guerin A, Aziz AS, Mutch C et al (2014) Pyridox(am)ine-5-phosphate oxidase deficiency treatable cause of neonatal epileptic encephalopathy with burst suppression: case report and review of the literature. J Child Neurol. doi: 10.1177/0883073814550829