PNPO and metabolic disease: We examined the genetic and metabolic disorders linked to vitamin B6 deficiency, such as mutations in pyridox(am)ine 5’-phosphate oxidase (PNPO), Aldehyde Dehydrogenase 7 Family Member A1 (ALDH7A1), alkaline locus phosphatase (ALPL), and cystathionine β-synthase (CBS), and discussed the clinical rationale for empirical administration in acute neonatal seizure settings.