Journal of Inherited Metabolic Disease

, Volume 32, Issue 2, pp 204–213

New treatment paradigms in neonatal metabolic epilepsies

SSIEM Symposium 2008

DOI: 10.1007/s10545-009-1045-8

Cite this article as:
Pearl, P.L. J Inherit Metab Dis (2009) 32: 204. doi:10.1007/s10545-009-1045-8


Neonatal seizures represent a major challenge among the epilepsies vis-à-vis seizure classification, electroclinical correlation, inherent excitability of neocortex, ontogenic characteristics of neurotransmitter receptors, and responsiveness to standard antiepileptic drugs. Each of these factors renders neonatal seizures more difficult to treat, and therapy has been a vexing area for recent advances in this seizure category. Conversely, specific metabolic disorders have very special therapeutic considerations in the clinical setting of neonatal seizures which require a high index of clinical suspicion and rapid intervention for a successful outcome. The prototype is pyridoxine dependency, although pyridoxal 5′-phosphate dependency is a recently recognized but treatable neonatal epilepsy that deserves earmarked distinction. Clinicians must remain vigilant for these possibilities, including atypical cases where apparent seizure-free intervals may occur. Folinic acid-dependent seizures are allelic with pyridoxine dependency. Serine-dependent seizures and glucose transporter deficiency may present with neonatal seizures and have specific therapy. A vital potassium channel regulated by serum ATP/ADP ratios in the pancreas and brain may be mutated with a resultant neuroendocrinopathy characterized by development delay, epilepsy, and neonatal diabetes (DEND). This requires oral hypoglycaemic therapy, and not insulin, for neurological responsiveness. The startle syndrome of hyperekplexia, which mimics neonatal epilepsy, has been associated with laryngospasm and sudden death but is treated with benzodiazepines.



5-hydroxyindoleacetic acid


α-aminoadipic semialdehyde


α-amino-3-hydroxy-5-methyl-4-isoxazole propionate


development delay, epilepsy, and neonatal diabetes


γ-aminobutyric acid


glutamic acid decarboxylase


homovanillic acid




pyridoxal 5-phosphate


pyridox(am)ine oxidase

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  1. 1.Department of Neurology, Neuroscience Center of Excellence and Clinical Research Institute, Children’s National Medical CenterGeorge Washington University School of MedicineWashingtonUSA
  2. 2.Clinical Epilepsy Branch, National Institute of Neurological Disorders and StrokeNational Institutes of HealthBethesdaUSA
  3. 3.Department of NeurologyChildren’s National Medical CenterWashingtonUSA