Abstracts

OBJECTIVE: Participants will learn about SSADH deficiency, a disorder of GABA metabolism, and gain diagnostic skills in the epilepsy and EEG characteristics of the syndrome.
RATIONALE: Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare metabolic encephalopathy which does not show a typical intermittent course with episodic decompensation. SSADH deficiency is a disorder of GABA metabolism characterized by detection of 4-OH-butyric aciduria with elevated CSF levels of GABA and [gamma]-hydroxybutyrate (GHB). Patients typically have mental retardation, predominant language impairment, nonprogressive ataxia, hypotonia, autistic features, and aggressive behaviors. While patients have been reported to have seizures, the frequency of seizures in this disorder, as well as associated semiology and EEG findings, have not been previously reported.
METHODS: We are following a group of 7 SSADH deficiency patients at our institution and report their seizure characteristics and EEG findings in this presentation. We also reviewed the world literature and report the epilepsy/EEG features in published cases.
RESULTS: Of our 7 patients, 3 have had seizures: all with GTCS, 1 with absence; convulsive status epilepticus has occurred in 2. EEG findings include diffuse and frontal background slowing, generalized spike-wave discharges with significant activation during sleep, and focal spike discharges in central/temporal areas. Sleep spindle asynchrony was noted in a 21 year old. Of 50 reported cases, 24 (48%) have had seizures. Of 25 cases with reported EEG, 6 had multifocal spikes, 2 with significant background slowing; 1 overnight study demonstrated a lack of stage REM sleep.
CONCLUSIONS: Patients with SSADH deficiency have an approximately 50% incidence of seizures, including absence and convulsive, and both generalized and focal epileptiform discharges on EEG. The pathophysiology of seizures in SSADH deficiency is unknown. These patients have high CSF levels of GABA and GHB. GHB, a GABA-B agonist, induces absence in animal models. Imaging studies have thus far revealed predominantly T2-MR hyperintensities in the globus pallidi as well as other white matter abnormalities and cerebellar vermian atrophy. PET and SPECT studies are underway to further elucidate neurometabolic abnormalities in this disorder. SSADH patients commonly have absence and convulsive seizures, and generalized and focal EEG discharges. Urinary organic acid analysis for the specific detection of 4-OH-butyric acid should be investigated in symptomatic epilepsies of unknown etiology.
[Supported by: NINDS NS-40270 (Dr.Gibson)]