4-HYDROXYBUTYRIC ACID AND THE CLINICAL PHENOTYPE OF SUCCINIC SEMIALDEHYDE DEHYDROGENASE-DEFICIENCY, AN INBORN ERROR OF GABA-METABOLISM

SSADH deficiency, a rare inborn error of human metabolism, disrupts th e normal metabolism of the inhibitory neurotransmitter GABA. In respon se to the defect, physiologic fluids from patients accumulate GHB, a c ompound with numerous neuromodulatory properties, Clinical and biochem ical findings in patients are contrasted with existing neuropharmacolo gic data on GHB in animals and men. We conclude that GHB contributes t o the pathogenesis of SSADH deficiency; whether this effect is mediate d by GHB, by GABA following metabolic interconversion, or via synergis tic mechanisms by both compounds, remains to be determined. An animal model of SSADH deficiency should further define the role of GHB in the pathogenesis of SSADH deficiency, and provide a useful vehicle for th e evaluation of new therapeutic intervention.