European Journal of Pediatrics

, Volume 168, Issue 6, pp 697–704

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

Authors

  • Gregory J. Basura
    • School of MedicineUniversity of Washington
    • Children’s Hospital and Regional Medical Center
  • Shawn P. Hagland
    • Seattle Children’s Hospital Research Institute
    • Department of Otolaryngology, Head and Neck SurgeryUniversity of North Carolina
  • Anna M. Wiltse
    • Departments of Neurology and PediatricsUniversity of California
    • School of PharmacyUniversity of Washington
    • Seattle Children’s Hospital Research Institute
    • Departments of Neurology and PediatricsUniversity of California
    • Departments of Neurology and Pediatrics, Center on Human Development and Disability, Center for Neurogenetics and NeurotherapeuticsUniversity of Washington
    • California Department of Mental Health
Original Paper

DOI: 10.1007/s00431-008-0823-x

Cite this article as:
Basura, G.J., Hagland, S.P., Wiltse, A.M. et al. Eur J Pediatr (2009) 168: 697. doi:10.1007/s00431-008-0823-x

Abstract

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.

Keywords

Pyridoxine-dependent seizuresPyridoxine-responsive seizuresALDH7A1AntiquitinPipecolic acidα-aminoadipic semialdehyde

Abbreviations

PDS

Pyridoxine-dependent seizures

PRS

Pyridoxine-responsive seizures

PA

Pipecolic acid

AASA

α-aminoadipic semialdehyde

P5P

Pyridoxal-5-phosphate

OCD

Obsessive compulsive disorder

AD

Autistic disorder

PDD

Pervasive developmental disorder, not otherwise specified

BPSU

British Paediatric Surveillance Unit

Copyright information

© Springer-Verlag 2008