JIMD Reports, Volume 27

Reid, Emma S, Williams, Hywel, Stabej, Polona Le Quesne, James, Chela, Ocaka, Louise, Bacchelli, Chiara, Footitt, Emma J, Boyd, Stewart, Cleary, Maureen A, Mills, Philippa B, Clayton, Peter T, 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, Reid, Emma S., Footitt, Emma J., Cleary, Maureen A., Mills, Philippa B., Clayton, Peter T.

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.