Summary Purpose:  Epilepsy is a commonly reported but rarely described clinical hallmark of mitochondrial respiratory chain defects (RCDs) with encephalopathy. Methods:  From 1990–2006 we collected data about 56 children with RCD (single, n = 24 or multiple, n = 20 mitochondrial complex deficiencies; mtDNA mutation, n = 11; mtDNA depletion n = 10 of 21; and nuclear gene mutation n = 11). Epileptic features were reviewed retrospectively. Results:  First seizures were frequently (47 patients, 82.5%) preceded by failure to thrive, psychomotor delay, ataxia, or multisystemic dysfunction. Sixty percent of the patients had several seizure types. Six age‐related epilepsy phenotypes could be identified: status epilepticus complicating neonatal multivisceral deficiency (2 patients), neonatal myoclonic encephalopathy (3 patients), infantile spasms (8 patients), refractory or recurrent status epilepticus (21 patients), epilepsia partialis continua (4 patients), and myoclonic epilepsy (18 patients). Except for infantile spasms, epilepsy was difficult to control in most patients (95%). Valproate was administered to 25 patients, one of whom developed acute liver failure 6 days later. Twenty‐two patients (45%) died, half of them within 9 months from the onset of epilepsy. Discussion:  In RCD, epilepsy is not only difficult to control but its occurrence often indicates a severe turn in the course of the disease. For one‐third of the patients, classical biochemical measures failed to reveal any abnormality and RCD could be detected in the liver only.

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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.