Biomarkers of mitochondrial dysfunction in autism spectrum disorder: A systematic review and meta-analysis.
Level 3 - non-randomized controlled study
Systematic review and meta-analysis of predominantly observational and case-control biomarker studies.
PubMed 38703861 · doi:10.1016/j.nbd.2024.106520
What was done
A systematic review and meta-analysis synthesized 204 published studies assessing biochemical, metabolic, and genetic biomarkers of mitochondrial dysfunction across various tissues (blood, peripheral blood mononuclear cells, lymphocytes, and brain) in individuals with autism spectrum disorder (ASD) versus controls.
What was found
Individuals with ASD showed significant elevations (all p < 0.01) in the prevalence of abnormal lactate (17%), pyruvate (41%), alanine (15%), and creatine kinase (9%). ASD cohorts differed significantly from controls (all p < 0.01; Cohen's d' ≥ 0.6) in mean pyruvate, lactate-to-pyruvate ratio, ATP, and creatine kinase. Meta-analyses identified significant differences (p < 0.01) in overall mitochondrial DNA (mtDNA) copy number and in ND1, ND4, and CytB genes. Several markers (lactate, pyruvate, carnitine, acyl-carnitines, CoQ10, and mtDNA variations) were associated with ASD severity and specific clinical features such as neurodevelopmental regression and gastrointestinal symptoms.
Why it matters
This review provides quantitative evidence that biochemical and genetic signatures of mitochondrial dysfunction characterize a substantial subset of individuals with ASD, highlighting potential pathways for biological subgrouping and targeted metabolic interventions.
Limits
The included studies showed substantial variability due to inconsistent sample collection and processing methodologies alongside inherent ASD phenotypic heterogeneity. The observational nature of the primary literature cannot establish whether mitochondrial alterations are causal or secondary phenomena, and clinical symptom associations were not consistently replicated across all reviewed studies.
Cited by
- supports Autism spectrum disorder is driven in part by mitochondrial dysfunction and a cerebral energy deficit.