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.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Aldehyde Oxidoreductases / cerebrospinal fluid
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Aldehyde Oxidoreductases / deficiency*
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Animals
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Anticonvulsants / pharmacology
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Anticonvulsants / therapeutic use
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Child
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Developmental Disabilities / etiology
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Disease Models, Animal
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Electroencephalography
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Humans
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Illicit Drugs / adverse effects
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Illicit Drugs / metabolism
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Metabolism, Inborn Errors / cerebrospinal fluid
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Metabolism, Inborn Errors / complications
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Metabolism, Inborn Errors / drug therapy
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Metabolism, Inborn Errors / physiopathology*
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Phenotype
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Sodium Oxybate* / adverse effects
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Sodium Oxybate* / metabolism
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Succinate-Semialdehyde Dehydrogenase
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Vigabatrin
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gamma-Aminobutyric Acid / analogs & derivatives
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gamma-Aminobutyric Acid / metabolism*
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gamma-Aminobutyric Acid / pharmacology
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gamma-Aminobutyric Acid / therapeutic use
Substances
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Anticonvulsants
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Illicit Drugs
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gamma-Aminobutyric Acid
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Sodium Oxybate
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Aldehyde Oxidoreductases
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ALDH5A1 protein, human
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Succinate-Semialdehyde Dehydrogenase
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Vigabatrin