LAUSR

We describe a neonate and a 14-month-old child presenting with seizures that were not (completely) controlled with anti-epileptic medications. There were no signs of infection and electrolytes and neuro-imaging were normal. In the neonate, pyridoxine was administered followed by cessation of seizures and a diagnosis of pyridoxine-dependent epilepsy (PDE-ALDH7A1, a neurometabolic disorder of lysine metabolism) was genetically confirmed. The 14-month-old child received a genetic diagnosis of PDE-ALDH7A1 after abnormalities in the metabolic investigations. Both children were treated with pyridoxine and adjunct lysine reduction therapy (LRT). Seizures were controlled completely, but both children are developmentally delayed. During her second pregnancy, the mother of the neonate was started on pyridoxine treatment due to the risk of PDE-ALDH7A1. After delivery, pyridoxine treatment was continued in the neonate, who did not show any clinical symptoms. Molecular analysis identified the familial mutations consistent with the diagnosis of PDE-ALDH7A1. Adjunct LRT was initiated. This child has never experienced seizures and development has been completely normal thus far (age 2.9 years), despite the shared genotype with their sibling with developmental delays.In conclusion, in neonates, infants and children presenting with seizures of unknown origin with partial or no response to common anti-epileptic medications, the diagnosis of PDE-ALDH7A1 or other pyridoxine responsive genetic epilepsies should be considered, prompting a trial of pyridoxine as 'diagnostic therapeuticum'. The digital application Treatable-ID (www.treatable-id.org) can support clinicians in the early diagnosis of treatable conditions in patients presenting with developmental delay/intellectual disability of unknown cause.