Photosensitive absence epilepsy with myoclonias and heterozygosity for succinic semialdehyde dehydrogenase (SSADH) deficiency

Objective Succinic semialdehyde dehydrogenase (SSADH) deficiency is a neurometabolic disorder characterized by excessive GABA levels and seizures. There has been no clinical phenotype described to date with heterozygosity for SSADH deficiency. Methods A patient heterozygous for SSADH deficiency presented with absence and myoclonic seizures. EEG monitoring and enzymatic, metabolic, and molecular studies for SSADH were obtained on the patient and family members. Results EEG recordings yielded generalized 3–4 Hz spike-wave paroxysms and trains of multiple spikes in the heterozygous patient, and photosensitivity in the heterozygous patient and parent as well as in the sibling with homozygous deficiency. The heterozygous patient and parents did not manifest 4-OH-butyric aciduria but SSADH levels were low and a splice site mutation of the SSADH gene was identified in each. Conclusions Heterozygosity for SSADH deficiency may be associated with an epilepsy syndrome characterized by absence and myoclonic seizures, photoparoxysmal EEG and generalized epileptiform discharges Significance Heterozygous SSADH deficiency may be suspected, given an appropriate family history in the setting of an apparently idiopathic generalized epilepsy. Pathogenic explanations may relate to regional elevations in GABA or GHB concentrations