Significant behavioral disturbances in succinic semialdehyde dehydrogenase (SSADH) deficiency (Gamma-Hydroxybutyric aciduria)

摘要: Abstract Background We report two adult patients with succinic semialdehyde dehydrogenase deficiency, manifesting as γ-hydroxybutyric aciduria. For both, the clinical presentation included significant behavioral disturbances and psychosis (hallucinations, disabling anxiety, aggressive behavior, sleep disorder), leading to multiple therapeutic attempts. Intervention benzodiazepines appeared most efficacious, resulting in decreased aggression agitation improvement anxiety. A review of 56 published unpublished studies SSADH-deficient revealed that 42% manifested disturbances, whereas 13% (predominantly adults) displayed psychotic symptomatology. Methods To explore potential biochemical basis these abnormalities, we studied cerebrospinal fluid derived from 13 patients, which significantly elevated GHB (65- 230-fold), high free total GABA (up threefold), low glutamine. Results Although within control range, homovanillic 5-hydroxyindoleacetic acids (end products dopamine serotonin metabolism, respectively) showed a linear correlation increasing concentration, suggesting enhanced turnover. Conclusions conclude combined glutamine suggest disruption glial-neuronal glutamine/GABA/glutamate shuttle necessary for replenishment neuronal neurotransmitters, altered metabolism may be causally linked hyperkinetic movement disorders seen patients.