Autism spectrum disorder and GABA levels in children with succinic semialdehyde dehydrogenase deficiency

Succinic semialdehyde dehydrogenase (SSADH) is an enzyme responsible for breaking down a molecule called GABA, which is very important for the brain's system of self-control (inhibitory functions). Deficiency of this enzyme, resulting from genetic mutations carried by both parents, leads to the inherited metabolic disorder termed SSADH deficiency. The increased concentrations in the brains of individuals with SSADH deficiency lead to an imbalance of the excitation and inhibition circuitries needed for proper brain development and function. In addition to intellectual disability, seizures, movement disorders, and behavioral problems, one of the consequences of this imbalance is autism spectrum disorder, which is common in individuals with this condition. The findings of our study showed that autism spectrum disorders are more likely to onset in people with SSADH deficiency beyond a relatively late age of 7 years 2 months and as plasma GABA levels drop below a level of ~2.5 μM. Knowledge of these cutoff values may be applicable for earlier diagnosis and management of autism spectrum disorders in this population. The findings of our study also support the notion that SSADH deficiency needs to be considered in the diagnostic evaluation of autism spectrum disorders, especially if autistic symptoms appear at an older age.