title: Neonatal vitamin-responsive epileptic encephalopathies.
abstract: The treatment of neonatal seizures generally relies on the use of one or more anticonvulsant medications along with evaluation and management of any underlying etiology. In some circumstances, neonatal seizures are refractory to therapy and result in poor outcomes, including death. Certain rare vitamin- responsive inborn errors of metabolism may present as neonatal encephalopathy with anticonvulsant-resistant seizures. Therefore, it is vital for the clinicians of caring for seizing encephalopathic newborns to consider these particular disorders early in the hospital course. Pyridoxine-dependent seizures are due to deficiency of alpha-aminoadipic semialdehyde dehydrogenase (antiquitin) which is encoded by ALDH7A1. Seizures in infants who are pyridoxine-dependent must be treated using pharmacologic doses of pyridoxine (vitamin B(6)), and life-long therapy is required. Despite medical therapy, developmental handicaps, particularly in expressive language, are common. Folinic acidresponsive seizures are treated with supplements of folinic acid (5-formyltetrahydrofolate). Recently, patients with this condition were also demonstrated to be antiquitin deficient. Pyridoxal phosphate-dependent seizures result from a deficiency of pyridox(am)ine 5'-phosphate oxidase which is encoded by PNPO. Patients with this cause of seizures respond to pyridoxal phosphate but not to pyridoxine. This review discusses our current understanding of these three neonatal vitamin-responsive epileptic encephalopathies and a diagnostic and treatment protocol is proposed.
authors.affiliation: Departments of Neurology and Pediatrics, the Center on Human Development and Disability, University of Washington, Seattle, WA, USA. sgospe@uw.edu
authors.forename: Sidney M
authors.initials: SM
authors.lastname: Gospe
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000235:genetics; D002657:Child Development; D004569:Electroencephalography; D006801:Humans; D007231:Infant, Newborn; D002955:Leucovorin / Q000627:therapeutic use*; D011732:Pyridoxal Phosphate / Q000627:therapeutic use*; D011736:Pyridoxine / Q000627:therapeutic use*; D012640:Seizures / Q000175:diagnosis / Q000188:drug therapy*
chemical_list: D011732:Pyridoxal Phosphate; C089507:ALDH7A1 protein, human; D000444:Aldehyde Dehydrogenase; D011736:Pyridoxine; D002955:Leucovorin