Abstracts

Rationale: Epilepsy is a common source of morbidity in Succinic Semialdehyde Dehydrogenase (SSADH) deficiency, a disorder of GABA degradation with elevated GHB.  Adult reports indicate worsening epilepsy and high SUDEP risk.  We report the epilepsy characteristics of SSADH deficiency from our longitudinal study. Methods: A longitudinal study obtains baseline and periodic six month follow-up data from patients in the SSADH registry.  Assessment measures include the MACS (manual ability), GMFCS (gross motor), ABAS (adaptive behavior), and QOL inventory in addition to seizure characteristics. Results: There are 129 subjects in the SSADH Registry; 44 are enrolled in the natural history study.  The age range of the registry population is 8 weeks to 63 years (median 7.75 y) (43% male). Epilepsy is present in 50% and more prevalent in the adolescent/adult cohorts: 70% (33/48) >12 years vs 37% (30/81) < 12 years (p<0.001). For the group in the longitudinal cohort, active epilepsy (>2 seizures/yr) increases with age: 52% (13/25) >12 years and 21% (4/19) <12 years (p=0.037). The most common seizure type was generalized tonic- clonic (32/64), followed by myoclonic (21/64) and absence (20/64). Of the patients in the registry, 91 reported having had an EEG, of which 35% were abnormal (32/91), with generalized epileptiform discharges (12/32) and diffuse slowing (10/32) being the most common abnormalities.To date we are aware of 4 deaths of patients diagnosed as probable SUDEP, two of which were adult patients in our registry (age 63 and 33) and two of which were not in the registry (age 19 and mid-20s). With 29 adult subjects in the registry, the SUDEP risk in this population would suggest a rate of 13% (4/31). Conclusions: Epilepsy is a co-morbid diagnosis in half of patients with SSADH deficiency and increases in incidence during adolescence and adulthood compared to early childhood presentation and diagnosis with hypotonia and developmental impairment.  Generalized seizure types and EEG abnormalities are predominant.  There appears to be a striking incidence of SUDEP.  Funding: No funding was received.