P 968. Vitamine B6-Dependent Epilepsy in a 14-Year-Old Girl with Drug-Resistant Seizures and Recurring Status Epilepticus

Background: Vitamine B6–dependent respectively pyridoxine-dependent epilepsy, in most cases caused by homozygous or compound heterozygous mutations in the ALDH7A1 gene, is a rare neurometabolic disease which usually begins in the first day of life. Only the immediate treatment with pyridoxine can stop the seizures.

Aims: We report the case of a 14-year-old female patient with global developmental delay and a drug-resistant epilepsy of unknown cause, in whom whole exome sequencing (WES) revealed a pyridoxine-dependent epilepsy.

Question: We discuss the role of WES for epilepsies with an atypical course which are drug resistant.

Methods: The first seizures are reported to have occurred at the age of 1 year and 10 months (on the basis of a difficult anamnesis). The girl had a global developmental delay with mental retardation and developed a drug-resistant epilepsy, which could not be controlled even by a complex combination of antiepileptic drugs.

At the age of 14 years, she presented with recurring status epilepticus and developed a severe encephalopathy. Due to the unknown etiology and the suspicion of a neurogenetic disease, a WES was conducted.

Results: The WES revealed two compound heterozygous missense mutations in the ALDH7A1 gene. The subsequent biochemical analysis confirmed the vitamin B6 (pyridoxine)-dependent epilepsy (significantly elevated levels of pipecolic acid, aminoadipate semialdehyde, and piperideine-6-carboxylic acid in the plasma, elevated levels of pipecolic acid in cerebrospinal fluid).

Having received the results of the molecular genetic testing, we began to treat the patient, which was in status epilepticus at that time, with pyridoxine in a high dose. The treatment led to freedom of seizures and a persisting clinical improvement which allowed the reduction of the previous antiepileptic medication. After 14 days of treatment with pyridoxine, the EEG showed only mild general abnormalities, no typical epileptic activity, and no ictal patterns.

Conclusions: In the case of a drug-resistant epilepsy, a pyridoxine-dependent epilepsy should be considered, even if the seizures began after the neonatal period, and the respective metabolic analysis should be repeated. Several recent publications (Al Tenejii et al, 2017; Wang et al, 2017; and Haidar et al, 2018) report, in accordance with our case, atypical courses and a great phenotypic variability with sporadic manifestation of the epilepsy after infancy. For drug-resistant epilepsies with and without developmental delay, WES is recommended to rapidly identify treatable causes.