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Mol Diagn Ther. 2018 Oct;22(5):571-593. doi: 10.1007/s40291-018-0352-x.

Clinical and Molecular Characteristics of Mitochondrial Dysfunction in Autism Spectrum Disorder.

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Department of Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children's Research Institute, Little Rock, AR, USA.
Section of Medical Genetics, Ochsner Health System, New Orleans, LA, USA.
Rossignol Medical Center, Aliso Viejo, CA, USA.
Department of Pediatrics, Neurology Section, St. Christopher's Hospital for Children, Drexel University College of Medicine, Philadelphia, PA, USA.
Division of Neurodevelopmental Disorders, Department of Neurology, Barrow Neurological Institute, Phoenix Children's Hospital, 1919 E Thomas St, Phoenix, AZ, USA.
Department of Child Health, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, USA.


Autism spectrum disorder (ASD) affects ~ 2% of children in the United States. The etiology of ASD likely involves environmental factors triggering physiological abnormalities in genetically sensitive individuals. One of these major physiological abnormalities is mitochondrial dysfunction, which may affect a significant subset of children with ASD. Here we systematically review the literature on human studies of mitochondrial dysfunction related to ASD. Clinical aspects of mitochondrial dysfunction in ASD include unusual neurodevelopmental regression, especially if triggered by an inflammatory event, gastrointestinal symptoms, seizures, motor delays, fatigue and lethargy. Traditional biomarkers of mitochondrial disease are widely reported to be abnormal in ASD, but appear non-specific. Newer biomarkers include buccal cell enzymology, biomarkers of fatty acid metabolism, non-mitochondrial enzyme function, apoptosis markers and mitochondrial antibodies. Many genetic abnormalities are associated with mitochondrial dysfunction in ASD, including chromosomal abnormalities, mitochondrial DNA mutations and large-scale deletions, and mutations in both mitochondrial and non-mitochondrial nuclear genes. Mitochondrial dysfunction has been described in immune and buccal cells, fibroblasts, muscle and gastrointestinal tissue and the brains of individuals with ASD. Several environmental factors, including toxicants, microbiome metabolites and an oxidized microenvironment are shown to modulate mitochondrial function in ASD tissues. Investigations of treatments for mitochondrial dysfunction in ASD are promising but preliminary. The etiology of mitochondrial dysfunction and how to define it in ASD is currently unclear. However, preliminary evidence suggests that the mitochondria may be a fruitful target for treatment and prevention of ASD. Further research is needed to better understand the role of mitochondrial dysfunction in the pathophysiology of ASD.

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