title: Myoclonic absence epilepsy with photosensitivity and a gain of function mutation in glutamate dehydrogenase.
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.
authors.affiliation: Service de Neurologie Pediatrique et Maladies Metaboliques, Departement de Pediatrie, Hopital Necker Enfants Malades, AP-HP, Université Paris Descartes, Paris, France. nadia.bahi-buisson@nck.ap-hop-paris.fr
authors.forename: Nadia
authors.initials: N
authors.lastname: Bahi-Buisson
authors.forename: Sandra
authors.initials: S
authors.lastname: El Sabbagh
authors.forename: Christine
authors.initials: C
authors.lastname: Soufflet
authors.forename: Fabienne
authors.initials: F
authors.lastname: Escande
authors.forename: Nathalie
authors.initials: N
authors.lastname: Boddaert
authors.forename: Vassili
authors.initials: V
authors.lastname: Valayannopoulos
authors.forename: Christine
authors.initials: C
authors.lastname: Bellané-Chantelot
authors.forename: Karine
authors.initials: K
authors.lastname: Lascelles
authors.forename: Olivier
authors.initials: O
authors.lastname: Dulac
authors.forename: Perrine
authors.initials: P
authors.lastname: Plouin
authors.forename: Pascale
authors.initials: P
authors.lastname: de Lonlay
mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D004569:Electroencephalography; D004831:Epilepsies, Myoclonic / Q000150:complications* / Q000235:genetics*; D005192:Family Health; D005260:Female; D005969:Glutamate Dehydrogenase / Q000235:genetics*; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D009154:Mutation; D010787:Photosensitivity Disorders / Q000209:etiology* / Q000235:genetics
chemical_list: D005969:Glutamate Dehydrogenase