Km. Gibson et al., VIGABATRIN THERAPY IN 6 PATIENTS WITH SUCCINIC SEMIALDEHYDE DEHYDROGENASE-DEFICIENCY, Journal of inherited metabolic disease, 18(2), 1995, pp. 143-146
The antiepileptic vigabatrin (gamma-vinyl GABA; 4-amino-5-hexenoic aci
d; Sabril) is an irreversible inhibitor of GABA-transaminase, the enzy
me responsible for the degradation of the neurotransmitter GABA. Vigab
atrin has been used therapeutically in five patients with succinic sem
ialdehyde dehydrogenase (SSADH) deficiency, a rare inborn error of GAB
A metabolism (McKusick 271980; Gibson et al 1989; Jaeken et al 1989; B
randt et al 1992; Howells et al 1992; Jakobs et al 1992; Uziel et al 1
993). SSADH-deficient patients accumulate increased quantities of 4-hy
droxybutyric 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 imp
rovement. In the five patients previously treated, there was an expect
ed increase in the cerebrospinal fluid (CSF) GABA/4-HBA ratio. Clinica
lly, there was improvement in ataxia, hypotonia, speech, behaviour, co
ncentration and cooperativity to differing degrees; one patient did no
t respond to therapy. We report our results of vigabatrin therapy in s
ix additional SSADH-deficient patients.