OBJECTIVE: Observational study using data collected from patients aged 2 to 5 years who were a subset of children participating in the Childhood
Autism Risk From Genes and Environment study in California, which is a population-based, case-control investigation with confirmed
autism cases and age-matched, genetically unrelated, typically developing controls, that was launched in 2003 and is still ongoing.
Mitochondrial dysfunction and
mtDNA abnormalities were evaluated in lymphocytes from 10 children with
autism and 10 controls.
MAIN OUTCOME MEASURES: The reduced
nicotinamide adenine dinucleotide (
NADH) oxidase activity (normalized to
citrate synthase activity) in lymphocytic mitochondria from children with
autism was significantly lower compared with controls (mean, 4.4 [95% confidence interval {CI}, 2.8-6.0] vs 12 [95% CI, 8-16], respectively; P = .001). The majority of children with
autism (6 of 10) had complex I activity below control range values. Higher plasma
pyruvate levels were found in children with
autism compared with controls (0.23 mM [95% CI, 0.15-0.31 mM] vs 0.08 mM [95% CI, 0.04-0.12 mM], respectively; P = .02). Eight of 10 cases had higher
pyruvate levels but only 2 cases had higher
lactate levels compared with controls. These results were consistent with the lower
pyruvate dehydrogenase activity observed in children with
autism compared with controls (1.0 [95% CI, 0.6-1.4] nmol × [min × mg
protein](-1) vs 2.3 [95% CI, 1.7-2.9] nmol × [min × mg
protein](-1), respectively; P = .01). Children with
autism had higher mitochondrial rates of
hydrogen peroxide production compared with controls (0.34 [95% CI, 0.26-0.42] nmol × [min × mg of
protein](-1) vs 0.16 [95% CI, 0.12-0.20] nmol × [min × mg
protein](-1) by
complex III; P = .02).
Mitochondrial DNA overreplication was found in 5 cases (mean ratio of
mtDNA to nuclear
DNA: 239 [95% CI, 217-239] vs 179 [95% CI, 165-193] in controls; P = 10(-4)). Deletions at the segment of
cytochrome b were observed in 2 cases (ratio of
cytochrome b to ND1: 0.80 [95% CI, 0.68-0.92] vs 0.99 [95% CI, 0.93-1.05] for controls; P = .01).
CONCLUSION: