Myoclonic absence epilepsy with photosensitivity and a gain of function mutation in glutamate dehydrogenase

Seizure. 2008 Oct;17(7):658-64. doi: 10.1016/j.seizure.2008.01.005. Epub 2008 Mar 5.

Abstract

Activating mutations in glutamate dehydrogenase (GDH), de novo or dominantly inherited, are responsible for the hyperinsulinism/hyperammonemia (HI/HA) syndrome. Epilepsy has been frequently reported in association with mutations in GDH, but the epilepsy phenotype has not been clearly determined. Here, we describe a family with a dominantly inherited mutation in GDH. The mother, brother and both sisters had myoclonic absence seizures, but only the mother and one sister had the complete HI/HA pattern. For the two sisters with myoclonic absences, epilepsy started during the second year of life while the brother, it started at 6 years. All 3 children showed the same EEG pattern characterized by photosensitive generalized and irregular spike-wave discharges and runs of multiple spikes. The mother's EEG recordings were normal without photosensitivity. Magnetic resonance imaging (MRI) and spectroscopy (MRS) were normal. A direct effect of the GDH mutation, perhaps in combination with recurrent hypoglycemia and chronic hyperammonemia could provide a pathophysiological explanation for the epilepsy observed in this syndrome and these are discussed.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Child
  • Child, Preschool
  • Electroencephalography
  • Epilepsies, Myoclonic / complications*
  • Epilepsies, Myoclonic / genetics*
  • Family Health
  • Female
  • Glutamate Dehydrogenase / genetics*
  • Humans
  • Infant
  • Magnetic Resonance Imaging / methods
  • Magnetic Resonance Spectroscopy / methods
  • Male
  • Mutation*
  • Photosensitivity Disorders / etiology*
  • Photosensitivity Disorders / genetics

Substances

  • Glutamate Dehydrogenase