Pyridoxal in the cerebrospinal fluid may be a better indicator of vitamin B6-dependent epilepsy than pyridoxal 5′-phosphate

Abstract Objectives We aimed to demonstrate the biochemical characteristics of vitamin B6 (VB6)-dependent epilepsy, with a particular focus on pyridoxal 5′-phosphate (PLP) and pyridoxal (PL) in the cerebrospinal fluid (CSF). Methods Using our laboratory database, we identified patients with VB6-dependent epilepsy and extracted their data on the concentrations of PLP, PL, pipecolic acid, α-aminoadipic semialdehyde, and monoamine neurotransmitters. We compared the biochemical characteristics of these patients with those of other epilepsy patients with low PLP and/or PL concentrations. Results We identified seven patients with pyridoxine-dependent epilepsy caused by ALDH7A1 gene abnormality, two patients with PLP homeostasis protein (PLPHP) deficiency, and 28 patients with other epilepsies with low CSF PLP and/or PL concentrations. CSF PL concentrations and PLP concentrations were low in patients with VB6-dependent epilepsy but CSF PL concentrations were not reduced in the majority of patients with other epilepsies with low CSF PLP concentrations. Elevation of 3-O-methyldopa and 5-hydroxytryptophan was demonstrated in some patients with VB6-dependent epilepsy, suggestive of PLP deficiency in the brain. Conclusions Low CSF PL concentrations may be a better indicator of PLP deficiency in the brain in VB6-dependent epilepsy than low CSF PLP concentrations. This finding is especially helpful in cases of suspected PLPHP deficiency, which does not have known biomarkers.