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Autistic spectrum disorders and mitochondrial encephalopathies

Autistic spectrum disorders (ASD) are common neurobehavioral syndromes characterized by deficits in social interactions, impaired communication skills and repetitive stereotypic behaviours expressed by 3 years of age (1). Recent studies of these disorders indicate a strong genetic component but specific aetiologies and pathogeneses are usually unknown (1–3). Concordance for ASD is 90% in identical twins compared to 10% for dizygotic twins and siblings. In recent years the incidence of ASD has increased throughout the world (4). Although changes in diagnosis might be a likely explanation, synergistic, environmental factors may account for part of the increased incidence of this serious disorder (5,6). In some cases, a disorder that includes autistic features is an identifiable syndrome due to a chromosomal abnormality (e.g. Fragile X), a single gene mutation (e.g. Rett’s Syndrome), an intrauterine infection (e.g. Rubella)or a metabolic disease (1). Mitochondrial cytopathies are among the metabolic disorders that continue to be associated with ASD in case reports (7–13). In larger series of people with autism but no diagnosis of a mitochondrial cytopathy, biochemical markers of mitochondrial dysfunction were found with variable frequency (14–17). These metabolic abnormalities may be elevated blood levels of lactate and pyruvate indicative of impaired aerobic glycolysis. In one study of 69 children, 20% had elevated blood lactates with five showing abnormalities at sites in the mitochondrial electron transport chain (17). In another study of 210 people, 17% had elevated blood lactates and 28% had elevated lactate/pyruvate ratios (15). The role of abnormal energy metabolism in the pathogenesis of autism might be related to the brain’s dependence on aerobic glycolysis (18). My colleagues and I recently have found support for the view that mitochondrial dysfunction contributes to the clinical phenotype of ASD. Lymphoblasts from autistic people who donated blood to the Autism Genetic Resource Ex-