VIGABATRIN THERAPY IN 6 PATIENTS WITH SUCCINIC SEMIALDEHYDE DEHYDROGENASE-DEFICIENCY

The antiepileptic vigabatrin (gamma-vinyl GABA; 4-amino-5-hexenoic acid; Sabril) is an irreversible inhibitor of GABA-transaminase, the enzyme responsible for the degradation of the neurotransmitter GABA. Vigabatrin has been used therapeutically in five patients with succinic semialdehyde dehydrogenase (SSADH) deficiency, a rare inborn error of GABA metabolism (McKusick 271980; Gibson et al 1989; Jaeken et al 1989; Brandt et al 1992; Howells et al 1992; Jakobs et al 1992; Uziel et al 1993). SSADH-deficient patients accumulate increased quantities of 4-hydroxybutyric acid (4-HBA) in physiological fluids. Inhibition of GABA-transaminase by vigabatrin should yield a decrease in the accumulation of 4-HBA in patient physiological fluids and may lead to clinical improvement. In the five patients previously treated, there was an expected increase in the cerebrospinal fluid (CSF) GABA/4-HBA ratio. Clinically, there was improvement in ataxia, hypotonia, speech, behaviour, concentration and cooperativity to differing degrees; one patient did not respond to therapy. We report our results of vigabatrin therapy in six additional SSADH-deficient patients.