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Neuropediatrics 1998; 29(1): 14-22
DOI: 10.1055/s-2007-973527
Review Articles

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

K. M. Gibson1 , 2 , C. F. Hoffmann3 , A. K. Hodson4 , T. Bottiglieri1 , 2 , C. Jakobs5
  • 1Institute of Metabolic Disease, Baylor University Medical Center, 3812 Elm Street
  • 2Department of Neurology, University of Texas Southwestern Medical Center, Dallas, Texas, USA;
  • 3Department of Neuropediatrics and Metabolic Diseases, Children's Hospital, University of Marburg, Germany;
  • 4Division of Neurology, Department of Pediatrics, Nemours Children's Clinic, Jacksonville, Florida;
  • 5Departments of Clinical Chemistry and Pediatrics, Academic Hospital, Free University Amsterdam, De Boelelaan 1117, Amsterdam HV 1081, The Netherlands
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Publication History

Publication Date:
12 March 2007 (online)

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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

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