Abstracts

Rationale: Taurine therapy has been proposed for succinic semialdehyde dehydrogenase (SSADH) deficiency due to partial GABA(A&B) receptor agonist effects and rescue in the null mouse model from status epilepticus and premature lethality. Physiologic biomarkers may be useful for evaluating therapeutic effects in pediatric neurotransmitters disorders. We tested the hypotheses that transcranial magnetic stimulation (TMS) would show decreased cortical excitability and that IQ testing would demonstrate cognitive improvement in patients on taurine. Methods: Biomarkers including neuropsychological testing, TMS, and CSF metabolites were studied in a cohort of patients on and off three months' taurine treatment. Results: Eight patients (6M/2F; age range 12-33 yrs) were enrolled. Neuropsychological results indicate baseline average Full Scale IQ of 44.1 (range 34-55), 3.6 SD below population mean. Of 6 who returned at 6-month follow-up, 5 completed cognitive testing (3M/2F) on therapy; average FS IQ = 43.4 (range 33-51). CSF biomarkers (n=4 subjects) revealed elevation in taurine levels, but no change in free or total GABA. Baseline cortical excitability measured with TMS agreed with previous findings in this population. Patients on taurine showed a decrease in cortical silent period and short interval intracortical inhibition. Conclusions: TMS demonstrated decreased inhibition in patients on taurine, in contrast to the study hypothesis, but consistent with its failure to produce clinical or cognitive improvement. TMS may be a useful biomarker for therapy in pediatric neurotransmitter disorders.