INTRODUCTION: Succinic semialdehyde dehydrogenase (SSADH) deficiency (gamma-hydroxybutyric aciduria) is a rare neurometabolic disorder of gamma-aminobutyric acid degradation. While neurological manifestations, such as developmental delay, are typical during infancy, limited data are available on adolescent and adult symptomatology. METHODS: We overview the phenotype of 33 adolescents and adults (10.1-39.5 years of age, mean: 17.1 years, 48% females) with SSADH deficiency. For this purpose, we applied a database with systematic questionnaire-based follow-up data. RESULTS: Sixty-six percent of patients (n=21) presented by 6 months of age, 14% from 6-12 months of age, 5% from 1-2 years of age, and 14% from 2-4 years of age, mean age at first symptoms was 11+/-12 months. However, mean age at diagnosis was 6.6+/-6.4 years of age. Presenting symptoms encompassed motor delay, hypotonia, speech delay, autistic features, seizures, and ataxia. Eighty-two percent demonstrated behavioral problems, such as attention deficit, hyperactivity, anxiety, or aggression, and 33% had >or=3 behavior problems. Electroencephalograms showed background slowing or epileptiform discharges in 40% of patients. Treatment approaches are then summarized. CONCLUSION: The variable phenotype in SSADH deficiency suggests the likelihood that this disease may be under-diagnosed. Families of patients with SSADH deficiency should be counseled and supported regarding the anticipated persistence of various neuropsychiatric symptoms into adulthood.
INTRODUCTION: Succinic semialdehyde dehydrogenase (SSADH) deficiency (gamma-hydroxybutyric aciduria) is a rare neurometabolic disorder of gamma-aminobutyric acid degradation. While neurological manifestations, such as developmental delay, are typical during infancy, limited data are available on adolescent and adult symptomatology. METHODS: We overview the phenotype of 33 adolescents and adults (10.1-39.5 years of age, mean: 17.1 years, 48% females) with SSADH deficiency. For this purpose, we applied a database with systematic questionnaire-based follow-up data. RESULTS: Sixty-six percent of patients (n=21) presented by 6 months of age, 14% from 6-12 months of age, 5% from 1-2 years of age, and 14% from 2-4 years of age, mean age at first symptoms was 11+/-12 months. However, mean age at diagnosis was 6.6+/-6.4 years of age. Presenting symptoms encompassed motor delay, hypotonia, speech delay, autistic features, seizures, and ataxia. Eighty-two percent demonstrated behavioral problems, such as attention deficit, hyperactivity, anxiety, or aggression, and 33% had >or=3 behavior problems. Electroencephalograms showed background slowing or epileptiform discharges in 40% of patients. Treatment approaches are then summarized. CONCLUSION: The variable phenotype in SSADH deficiency suggests the likelihood that this disease may be under-diagnosed. Families of patients with SSADH deficiency should be counseled and supported regarding the anticipated persistence of various neuropsychiatric symptoms into adulthood.
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