title: 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 bio-chemical 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.
authors.affiliation: Institute of Metabolic Disease, Baylor University Medical Center, Dallas, Texas, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Gibson
authors.forename: G F
authors.initials: GF
authors.lastname: Hoffmann
authors.forename: A K
authors.initials: AK
authors.lastname: Hodson
authors.forename: T
authors.initials: T
authors.lastname: Bottiglieri
authors.forename: C
authors.initials: C
authors.lastname: Jakobs
mesh_terms: D000445:Aldehyde Oxidoreductases / Q000134:cerebrospinal fluid / Q000172:deficiency*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use; D002648:Child; D002658:Developmental Disabilities / Q000209:etiology; D004195:Disease Models, Animal; D004569:Electroencephalography; D006801:Humans; D013287:Illicit Drugs / Q000009:adverse effects / Q000378:metabolism; D008661:Metabolism, Inborn Errors / Q000134:cerebrospinal fluid / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D010641:Phenotype; D012978:Sodium Oxybate / Q000009:adverse effects / Q000378:metabolism; D050644:Succinate-Semialdehyde Dehydrogenase; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D013287:Illicit Drugs; D005680:gamma-Aminobutyric Acid; D012978:Sodium Oxybate; D000445:Aldehyde Oxidoreductases; C493643:ALDH5A1 protein, human; D050644:Succinate-Semialdehyde Dehydrogenase; D020888:Vigabatrin