Pyridoxine-dependent epilepsy: case report

Introduction: Pyridoxine-dependent epilepsy is a very uncommon type of epilepsy. It is characterized by seizures that are not manageable with conventional anticonvulsive therapy, but respond clinically and electrophysically to pyridoxine therapy. Genetic analysis shows autosomal recessive mutations in ALDH7A1 gene. Enzymatic loss of α-aminoadipate-semialdehyde-dehydrogenase activity results in an accumulation of piperidine-6-carboxylate, which reacts with pyridoxal phosphate to a biologically inactive form. Subsequently, pyridoxal phosphate is no longer available for the metabolism of neurotransmitters.

Case Report: A 7-day-old male newborn was transferred to our clinic of recurrent clonic seizures.

In the final stages of pregnancy, rhythmic fetal movements were noticed. Delivery was uneventful. Furthermore, the baby showed a high startle response, a meteoritic abdomen and recurrent vomiting. The EEG displayed a focal sharp-wave activity synchronistic to multifocal myoclonic seizures.

The number of seizures could not be reduced under treatment with phenobarbital and lorazepam. We administered 100 mg of pyridoxine intravenously whereupon the seizures stopped immediately. The EEG after administration of pyridoxine turned into normal. Further analysis displayed an increased amount of urinary pipecolic acid/creatinine. (57µmol/mol creatinine, norm: 0.5 to 7µmol/mol creatinine). Genetic analysis revealed a previously described compound heterozygous mutation in exon 6 and an unknown mutation in exon 15 of the ALDH7A1 gene. Under daily oral pyridoxine administration (15 to 20 mg/kg) no more seizures occurred and until now the patient shows an appropriate neurological development.

Conclusion: The disappearance of seizures and loss of pathological EEG findings under treatment with pyridoxine provide clinical evidence for pyridoxine-dependent epilepsy. Biochemical and genetic proof for the final diagnosis is however necessary for lifetime therapy. Pyridoxine should be started as early as possible in case of therapy-resistant seizures in newborns.