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Mitochondrial dysfunction in autism spectrum disorders: A systematic review and meta-analysis – Source: Molecular Psychiatry, Jan 25, 2011

  [ 13 votes ]   [ Discuss This Article ]
By Daniel A Rossignol, Richard E Frye • • January 27, 2011

[Note: the mitochondria are central to cellular power generation and other cellular processes. Roughly, mitochondrial disease refers to a group of neuromuscular diseases generally associated with inherited mutations of mitochondrial DNA. Mitochondrial dysfunction refers to some impairment of mitochondrial function potentially associated with a range of different stressors, from inflammation and oxidative stress to toxin exposures.]

A comprehensive literature search was performed to collate evidence of mitochondrial dysfunction in autism spectrum disorders (ASDs) with two primary objectives.

First, features of mitochondrial dysfunction in the general population of children with ASD were identified.

Second, characteristics of mitochondrial dysfunction in children with ASD and concomitant mitochondrial disease (MD) were compared with published literature of two general populations: ASD children without MD, and non-ASD children with MD.

• The prevalence of mitochondrial disease (MD) in the general population of autism spectrum disorders was 5.0% (95% confidence interval 3.2, 6.9%), much higher than found in the general population (0.01%). [One in 20 vs. one in 10,000]

• The prevalence of abnormal biomarker values of mitochondrial dysfunction was high [up to one in three] in ASD, much higher than the prevalence of mitochondrial disease (MD). Variances and mean values of many mitochondrial biomarkers (lactate, pyruvate, carnitine and ubiquinone [Coenzyme Q10]) 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 with 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,

- Coenzyme 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.

Overall, this evidence supports the notion that mitochondrial dysfunction is associated with ASD. Additional studies are needed to further define the role of mitochondrial dysfunction in ASD.

Source: Molecular Psychiatry, Jan 25, 2011. PMID: 21263444, by Rossignol DA, Frye RE. International Child Development Resource Center, Melbourne, Florida; Division of Child and Adolescent Neurology and Children's Learning Institute, Department of Pediatrics, University of Texas Health Science Center at Houston, Texas, USA. [Email:]

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