Abstracts

Rationale: Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare disorder of GABA degradation featuring global developmental delay, hypotonia, epilepsy, extrapyramidal manifestations, hyporeflexia, and abnormal MRI signal involving the globus pallidus, subthalamic nucleus, and cerebellar dentate nuclei. The incidence is unknown and past estimates derive from laboratory reports of GHB aciduria, the biochemical marker. Delayed and under-diagnosis are suspected. Methods: Cross sectional analysis using a patient database combined with literature review was used to ascertain the number of all identifiable cases, age at diagnosis, and geographic distribution. Results: Overall, we identified 180 unique cases of SSADH deficiency dating back to Jakobs, Bojasch et al. in 1981 (91 confirmed subjects derived from our database and 89 with clinical details provided from the literature) from 39 countries. The largest proportions were from the US (24%), Turkey (10%), China (7%), Saudi Arabia (6%), and Germany (5%). All countries are shown in figure 1. The median age of diagnosis is 2 years, although 10% of cases are diagnosed in adolescence or adulthood. An adult was recently diagnosed at age 62 during a terminal illness marked by repeated status epilepticus. Three cases of SUDEP have been reported from our adult cohort (N = 35). Conclusions: A total of 180 unique cases of diagnosed SSADH deficiency could be confirmed, spread across 39 countries. Five reporting countries account for approximately half of all reported patients. With China and India accounting for ~36% of the world population, our data strongly suggest dramatic underreporting. Increased detection is anticipated in SSADH and similar rare disorders with the expansion of next generation gene sequencing. Additionally, there appears to be a high rate of SUDEP. The clinical evolution of the disease is unknown, and a longitudinal study of patients is planned to address this gap in our understanding. Funding: Internal Funding