Epilepsy is a typical symptom of inherited glycosylphosphatidylinositol deficiency (IGD) that often follows a drug-resistant course. High-dose pyridoxine therapy has been reported to be effective in selected cases of IGD-associated drug-resistant epilepsy. Most reports of effective outcomes describe treatment initiated in childhood, and data on treatment initiation in adulthood remain limited. A 22-year-old woman received high-dose pyridoxine therapy. She was being treated with high-dose phenobarbital (290 mg/day), with a blood concentration of 100 μg/mL, along with four anti-seizure medications, including topiramate, perampanel, zonisamide, and clonazepam. Her seizure frequency fluctuated, and she experienced more than 10 seizures per day, indicating inadequate control. A targeted exome sequencing panel identified compound heterozygous variants in the PIGO gene. Pyridoxine was started at a dose of 15 mg/kg/day and increased to 30 mg/kg/day 2 weeks later. Following the initiation of pyridoxine treatment, the patient experienced no clinical seizures during hospitalization. She exhibited no obvious side effects such as vomiting or liver dysfunction. At 1 year after introduction, the seizure frequency improved to only several times per month. In the present case of refractory epilepsy associated with IGD, high-dose pyridoxine therapy effectively controlled epileptic seizures and was administered without notable adverse events. In recent years, the increased use of genetic testing, including whole-exome sequencing, has led to an increase in early-diagnosed cases. Further data accumulation is necessary to evaluate outcomes in cases diagnosed and treated early in childhood and those diagnosed and treated in adulthood, as in the present case.
Yamamoto et al. (Wed,) studied this question.