Abstracts

Rationale: SSADH deficiency is an autosomal recessive inherited defect in GABA degradation leading to high exogenous levels of GABA and GHB. The aminoacid taurine has shown survival benefits in the SSADH null mouse model. Taurine has neuromodulatory actions and interacts with GABA-A and -B receptors. Following a case report of improvement in a 2-year-old boy with SSADH deficiency, we conducted an open label trial of taurine in SSADH deficiency.Methods: Subjects have been titrated weekly from 50mg/kg/day until reaching a target dose of 200mg/kg/day to a maximum dosage of 16 grams/day. The Adaptive Behavior Assessment Scale-II (ABAS-II) is administered at baseline and following six and twelve months of therapy. We used linear longitudinal modeling to compare ABAS scores during the period pre to the time-averaged scores in the period during taurine use. The model adjusted variance estimates, analogous to a paired t-test, to account for the correlation of scores within the same participant.Results: Twelve patients have been recruited: 6M/6F, age range at enrollment 5-28 yrs (mean 13yrs). One patient had a serious adverse event on 16 grams/day (hospitalization for hypersomnia). This led to a dose lowering paradigm with a new maximum daily dose of 10 grams. The taurine has been otherwise well-tolerated. Six subjects have completed the trial; 3 withdrew early due to perceived lack of efficacy. There have been no significant changes between pre- and Rx-composite scores in general adaptive, conceptual, practical, or social skills. However, a borderline lower score was observed on the conceptual (p=0.1) index during taurine use. Conclusions: Taurine is an aminosulfonic acid sold as a dietary supplement and has neuromodulatory, osmoregulatory, and tropic roles. It may have a protective role against retinal toxicity associated with vigabatrin, an irreversible inhibitor of GABA-transaminase leading to elevated GABA levels. Taurine has shown benefit in the SSADH deficient mouse model. This open-label pilot trial of taurine in patients with SSADH deficiency did not lead to demonstrable improvement in adaptive neurobehavioral functioning.