Objectives: In this presentation, we systematically review the evidence for mitochondrial dysfunction in ASD. First, features of mitochondrial dysfunction in the general population of children with ASD are identified. Second, characteristics of mitochondrial dysfunction in children with ASD and concomitant mitochondrial disease (MD) are compared to ASD children without MD, and non-ASD children with MD.
Methods: A comprehensive literature search of PUBMED, Google Scholar, CINAHL, EmBase, Scopus, and ERIC databases from inception through August 2010 was conducted to collate biochemical markers and other features that could indicate mitochondrial dysfunction in ASD. A meta-analysis was performed based on the information derived from these studies.
Results: The prevalence of MD in the general population of ASD was 5.0% (95% CI 3.2-6.9%), much higher than found in the general population (~0.01%). The prevalence of abnormal biomarker values of mitochondrial dysfunction was high in ASD, much higher than the prevalence of MD. Variances and mean values of many mitochondrial biomarkers (lactate, pyruvate, carnitine and ubiquinone) were significantly different between ASD and controls. Some markers correlated with ASD severity. Neuroimaging, in vitro, and post-mortem brain studies were consistent with an elevated prevalence of mitochondrial dysfunction in ASD. Taken together, these findings suggest children with ASD have a spectrum of mitochondrial dysfunction of differing severity. Eighteen publications representing a total of 112 children with ASD and MD (ASD/MD) were identified. The prevalence of developmental regression (52%), seizures (41%), motor delay (51%), gastrointestinal abnormalities (74%), female gender (39%), and elevated lactate (78%) and pyruvate (45%) was significantly higher in ASD/MD compared to the general ASD population. The prevalence of many of these abnormalities was similar to the general population of children with MD, suggesting that ASD/MD represents a distinct subgroup of children with MD. Most ASD/MD cases (79%) were not associated with genetic abnormalities, raising the possibility of secondary mitochondrial dysfunction. Treatment studies for ASD/MD were limited, although improvements were noted in some studies with carnitine, co-enzyme Q10, and B-vitamins. Many studies suffered from limitations, including small sample sizes, referral or publication biases, and variability in protocols for selecting children for MD workup, collecting mitochondrial biomarkers, and defining MD.
Conclusions: Overall, this evidence supports the hypothesis that mitochondrial dysfunction is associated with ASD. Additional studies are needed to further define the role of mitochondrial dysfunction in ASD.