Investigators at the Clinical Epilepsy and Neurorehabilitation Sections, NIH, Bethesda, MD; Albert Ludwigs University, Freiberg, Germany; and Children's National Medical Center, Washington, DC used transcranial magnetic stimulation (TMS) to quantify the excitation and inhibition in primary motor cortex in 8 patients (mean age 15.4 years) with succinic semialdehyde dehydrogenase (SSADH) deficiency. All patients were severely affected and many showed symptoms of ADHD and anxiety. Long interval intracortical inhibition was significantly reduced and the cortical silent period was significantly shortened in patients with SSADH deficiency compared to heterozygous parents and controls. Long interval intracortical inhibition and cortical silent period are thought to reflect GABA receptor-mediated inhibitory circuits, pointing to a GABA-ergic motor cortex dysfunction in patients with SSADH deficiency. [1]

COMMENT. SSADH deficiency is a rare autosomal recessive disorder of GABA degradation with elevation of gamma-hydroxybutyric acid and GABA. Infants present with developmental delay, hypotonia, retardation, ataxia, seizures, hyperkinetic behavior, aggression, and sleep disturbances. Urine organic acids show 4-hydroxybutyric/gamma-hydroxybutyric aciduria. MRI may show globus pallidus T2 abnormalities. TMS may be helpful in detection of homozygous carriers and in diagnosis of SSADH deficiency.