The spectrum of pyridoxine dependent epilepsy across the age span: A nationwide retrospective observational study

Abstract

Background Pyridoxine-dependent epilepsy (PDE) is a rare seizure disorder usually presenting with neonatal seizures. Most cases are caused by biallelic pathogenic ALDH7A1variants. While anti-seizure medications are ineffective, pyridoxine provides seizure control, and dietary interventions may be of benefit. As the natural history beyond adolescence is insufficiently explored, our study aimed to assess the spectrum of PDE at various ages in Norway. Methods Patients were ascertained by contacting all Norwegian paediatric, neurological, and neurohabilitation departments and relevant professional societies. Medical records were collected and reviewed. Results We identified 15 patients treated for PDE; 13 had ALDH7A1 variants (PDE-ALDH7A1), one had PNPO deficiency, and in one, aetiology remained obscure. Of those with PDE-ALDH7A1, 12 were alive at time of study; five were > 18 years old and six were 1 h) or uncertain effect. Median delay from first seizure to continuous treatment was 11 days (range 0–42). Nine experienced breakthrough seizures with intercurrent disease or due to pyridoxine discontinuation. Cognitive outcomes ranged from normal to severe intellectual disability. The condition appeared to remain stable in adult life. Significance We found a much higher prevalence of PDE-ALDH7A1 in children relative to adults, suggesting previous underdiagnosis and early mortality. Perinatal complications are common and can delay diagnosis and initiation of pyridoxine treatment. Lifelong and continuous treatment with pyridoxine is imperative. Due to better diagnostics and survival, the number of adult patients is expected to rise.

The spectrum of pyridoxine dependent epilepsy across the age span: A nationwide retrospective observational study