Metabolic disorders and abnormalities associated with autism spectrum disorder

Abstract

Recent research has implicated systematic physiological and metabolic abnormalities, such as immune dysregulation, inflammation, oxidative stress, mitochondrial dysfunction and other metabolic disorders that transcend organ specific dysfunction in ASD. In this context, ASD may arise from, or at least involve, systemic physiological abnormalities. In this review, common, and not so common, metabolic abnormalities associated with ASD are outlined. Mitochondrial dysfunction and cerebral folate abnormalities are the most prevalent metabolic disorders affecting children with ASD. Other potentially important metabolic disorders that have been reported in ASD include urea cycle disorders, succinic semialdehyde dehydrogenase deficiency, adenylosuccinate lyase deficiency, phenylketonuria, creatine deficiency syndromes, pyridoxine dependent and responsive seizures, biotinidase deficiency and Smith-Lemli-Opitz syndrome. Other metabolic abnormalities that appear to be associated with ASD are disorders of general cholesterol metabolism and tetrahydrobiopterin metabolism. Although detailed cases of children with ASD and these latter two metabolic abnormalities have not been formally described, there is evidence that some children with ASD may manifest these metabolic abnormalities. Lastly, an algorithm for systematically approaching the diagnosis of metabolic disease in ASD is provided.

Keywords

Autism spectrum disorder - mitochondrial disease - cerebral folate deficiency - folate receptor autoantibodies - metabolic disease