DNA Methylation Associated with Mitochondrial Dysfunction in a South African Autism Spectrum Disorder Cohort.
Sofia Stathopoulos, Renaud Gaujoux, Zander Lindeque and 4 others
PMID 32490597WHAT IT FOUND
South African children with autism showed altered DNA methylation in genes controlling mitochondrial energy production.
Urine tests revealed elevated organic acids linked to respiratory chain defects. These findings suggest mitochondrial dysfunction is a biological feature in this cohort, though no treatment was tested.
Key findings
01Differentially methylated genes were enriched in mitochondrial metabolic pathways, with eight of nine enriched pathways occurring primarily in the mitochondria.
02Urine analysis showed three metabolites (3-methylglutaconic acid, 3-hydroxy-3-methylglutaric acid, and ethylmalonic acid) were markedly elevated in the autism group compared to controls.
03The gene PCCB, involved in mitochondrial ATP metabolism, was differentially methylated in all three DNA methylation assays used.
STILL TO COME
How it was doneWhat they found
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What it does not show
The sample size was small, particularly for the initial DNA methylation screen (48 children), resulting in low statistical power (estimated 20%) to detect many true methylation differences. The study only included prepubertal boys in the methylation analysis, excluding girls and older adolescents, which limits generalizability. DNA was extracted from buccal cells, which may not perfectly reflect methylation patterns in the brain. The study reports associations between methylation and metabolites but did not measure gene expression or protein levels in the same tissue to prove a direct functional link. Seventeen children with ASD were excluded from the epigenetic analysis because they could not provide a DNA sample or had other neurodevelopmental disorders.
Declared interests
The authors declared no conflicts of interest. The study was funded by the South African Medical Research Council and the National Research Foundation.
The easy way to misread this
Do not interpret these findings as evidence that mitochondrial dysfunction causes autism or that mitochondrial supplements treat it. The study identifies a biological association in a small, specific group of boys, but does not test any intervention or prove that these methylation changes lead to symptoms.