Abstracts

SSADH deficiency is a disorder of GABA catabolism characterized by supraphysiologic levels of GABA and GHB, the latter an endogenous GABA metabolite. Drop attacks, cataplexy, tremors, and myoclonus have been reported in human GHB intoxication. The latter is a growing problem in the US population. We report the seizure data, EEG findings, and movement disorders observed in our expanding patient database of SSADH deficiency. We have a database of 81 patients with SSADH deficiency, comprised of 40 patients in our practice population or in whom we have collected systematic questionnaire data, and 41 patients with detailed published case reports. We analyzed this data for presence of seizures and seizure type(s), EEG abnormalities, and extrapyramidal movement disorders. Of 81 patients, 40 (50%) had seizures: 15 tonic-clonic; 10 absence; 7 myoclonic; 2 partial; 1 atonic; 1 ALTE; 18 unclassified. Of 40 patients with EEG data, 28 (70 %) were abnormal: 17 with background slowing; 11 generalized epileptiform discharges; 6 focal discharges; 2 photoparoxysmal response. Of 81 patients, 8 patients (10%) had prominent extrapyramidal manifestations (chorea, athetosis, dystonia, myoclonus). The mean age of onset in this cohort was 2.2 yrs (median 12 mos), vs 4.2y in the total group. In 4, the clinical course was consistent with a progressive encephalopathy, with regression or decompensation. In contrast, seizure onset was widely variable, from infancy to early adulthood, and most patients followed a static appearing course. Our expanding SSADH deficiency database enables a wider and more accurate description of the phenotype of this hyperGABAergic disorder. Half of SSADH deficient patients have seizures, which are usually generalized when classifiable. Nearly 75% of patients will have abnormal EEGs, with background slowing, generalized[gt]focal spikes, and occasionally photosensitivity. Patients with prominent movement disorders appear to have a more severe phenotype, and manifest some features seen also with acute GHB intoxication. Treatment strategies for seizures and movement disorders in SSADH deficiency may have therapeutic relevance to the growing problem of illicit GHB use. (Supported by NIH: NS40270, Epilepsy Foundation of America, Pediatric Neurotransmitter Disease Association)