Clinical features and the management of pyridoxine-dependent and pyridoxine-responsive seizures: review of 63 North American cases submitted to a patient registry

To facilitate clinical research on pyridoxine-dependent seizures (PDS), a rare disease registry was established for affected patients in the United States and Canada. From 1999 to 2007, 63 cases, ranging in age from 11 months to 40 years, were registered. All registered cases were diagnosed with PDS by their physicians using clinical criteria. Seventy percent of the cases presented with neonatal seizures, and the mean lag time between presentation and diagnosis was 313 days. Pyridoxine treatment regimens were varied, ranging from 50 to 2,500 mg per day (1.4 to 67.8 mg/kg/day). While 47 of the cases were seizure-free on pyridoxine monotherapy, over time, eight other cases also required the concomitant use of anticonvulsants for effective seizure control, while the remainder continued to have recurrent seizures, despite the use of pyridoxine and multiple anticonvulsants. Our review of this collection of cases suggests that, for some registered individuals, either pyridoxine may be acting as an adjunctive anticonvulsant or the patient may have developed a secondary etiology for seizures. In addition, some of these cases may have pyridoxine-responsive seizures (PRS) rather than pyridoxine-dependency. Four adult and seven school-aged cases were described as developmentally normal, while the other cases had a variety of neurodevelopmental handicaps. Twenty-five percent of the cases required the pharmacologic treatment of behavioral symptoms. Clinicians caring for neonates and other young patients with intractable seizures do not necessarily consider PDS as an etiology; therefore, certain cases may be undiagnosed or diagnosed late in the course of their evaluation and treatment. As the diagnosis of PDS can now be confirmed by genetic and biochemical testing, formal screening protocols for this disorder should be developed. Patients previously diagnosed with PDS by clinical criteria should also receive confirmatory testing.