Pyridoxine dependent epilepsies: new therapeutical point of view

Abstract Pyridoxine dependent epilepsies (PDEs) are rare autosomal recessive disorders with onset in neonatal period. Seizures are typically not responsive to conventional antiepileptic drugs, but they cease after parental pyridoxine administration. Atypical forms are characterized partly response to pyridoxine and a late onset of symptoms (up to the age of three years). Prevalence is variable and it has rarely been described. The genes involved in PDEs are the gene encoding for the Alpha-aminoadipic-semialdehyde dehydrogenase (ALDH7A1) and PROSC gene, which encodes a pyridoxal-5-phosphate binding protein. Mutations in the gene encoding for the pyridoxal-5′-phosphate oxidase enzyme (PNPO) are responsible of a clinical entity similar to PDEs responsive to pyridoxal-5-phosphate administration not to pyridoxine administration. PDEs diagnosis is often delayed because they are suspected only after conventional anticonvulsant drugs resistance. Herein authors aim to present an expert point of view on PDEs in childhood, reviewing the most recent literature data and proposing a new therapeutical approach for seizures of unknown origin in all those children up to the age of three years