Neurodevelopmental pattern of succinic semialdehyde dehydrogenase deficiency (gamma-hydroxybutyric aciduria).
Succinic semialdehyde dehydrogenase (SSADH deficiency) (MIM 271980) is a defect in gamma-aminobutyric acid catabolism, resulting in the accumulation of gamma-hydroxybutyric acid (GHB) and causing neurological and cognitive disorders of varying severity. The non-specific nature and the difficulties in detection of urinary GHB explain why this disorder is largely underdiagnosed. Of 350 patients identified worldwide, to date only six adults with SSADH deficiency have been reported in the literature. Here we describe two additional cases in brothers up to ages 26 and 28 years. This retrospective report sheds light on the clinical features of SSADH deficiency in relation to the physiopathological involvement of GHB, and tries to identify the specific neurodevelopmental pattern of this learning disability.* Features of this are: early impaired psychomotor development with hypotonia and disturbances in motor coordination; impaired development of language, mainly due to poor auditory perception; and seizures and psychotic features in late adolescence or adulthood. Moreover, narcolepsy-like symptoms could be a consistent feature of the disease.
Institut National de la Santé et de la Recherche Médicale U393, Hôpital Necker-Enfants Malades, Paris, France. kinabalu@free.fr
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A
Philippe
J
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Deron
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Geneviève
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de Lonlay
K M
KM
Gibson
D
D
Rabier
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Munnich
D000293:Adolescent; D000445:Aldehyde Oxidoreductases / Q000172:deficiency* / Q000378:metabolism; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007805:Language Development Disorders / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008661:Metabolism, Inborn Errors / Q000378:metabolism* / Q000503:physiopathology; D011618:Psychotic Disorders / Q000378:metabolism / Q000503:physiopathology; D035781:Siblings; D012893:Sleep Wake Disorders / Q000378:metabolism / Q000503:physiopathology; D050644:Succinate-Semialdehyde Dehydrogenase; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D005680:gamma-Aminobutyric Acid; D000445:Aldehyde Oxidoreductases; C493643:ALDH5A1 protein, human; D050644:Succinate-Semialdehyde Dehydrogenase