4-Hydroxybutyric Acid and the Clinical Phenotype of Succinic Semialdehyde Dehydrogenase Deficiency, an Inborn Error of GABA Metabolism

Abstract

SSADH deficiency, a rare inborn error of human metabolism, disrupts the normal metabolism of the inhibitory neurotransmitter GABA. In response to the defect, physiologic fluids from patients accumulate GHB, a compound with numerous neuromodulatory properties. Clinical and biochemical findings in patients are contrasted with existing neuropharmacologic data on GHB in animals and men. We conclude that GHB contributes to the pathogenesis of SSADH deficiency; whether this effect is mediated by GHB, by GABA following metabolic interconversion, or via synergistic 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 the evaluation of new therapeutic intervention.

Key words

4-Hydroxybutyric acid - GABA - Succinic semialdehyde dehydrogenase deficiency - Pathogenesis - Neurotransmitter - Mental retardation - Anaesthetic - Narcolepsy - Electroencephalogram - Seizure