MitoAction tele-call on ASD and mito

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Do you suspect mitochondrial dysfunction in your ASD child? Or do you just want to learn more about this topic, to see if it may be relevant for your child?

Please join MitoAction on Tuesday, January 11, 2011 at 12:30 pm EST for an informal discussion of an article titled, Mitochondrial Dysfunction in Autism, published in December 2010 Journal of American Medical Association (JAMA).

Mitochondrial Dysfunction in Autism

Written by: Giulivi C., Zhang YF, Omanska-Klusek A, Ross-Inta C, Wong S, Hertz-Picciotto I, Tassone F, Pessah IN

Abstract:

CONTEXT: Impaired mitochondrial function may influence processes highly dependent on energy, such as neurodevelopment, and contribute to autism. No studies have evaluated mitochondrial dysfunction and mitochondrial DNA (mtDNA) abnormalities in a well-defined population of children with autism.

OBJECTIVE: To evaluate mitochondrial defects in children with autism.

DESIGN, SETTING, AND PATIENTS: 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: Oxidative phosphorylation capacity, mtDNA copy number and deletions, mitochondrial rate of hydrogen peroxide production, and plasma lactate and pyruvate.

RESULTS: 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: In this exploratory study, children with autism were more likely to have mitochondrial dysfunction, mtDNA overreplication, and mtDNA deletions than typically developing children.

Research in this area is still evolving and the connection between the two diseases, although recognized for over a decade, is rapidly gaining traction and attention.

Calls on the link between ASD and mitochondrial disease take place every 2nd Tuesday of the month at 12:30 pm EST. To participate in this resource-share by telephone, please call, 1- and enter code 017921# at the prompt.

All are welcome. Please feel free to forward this announcement to other interested families.

For more information on mitochondrial disease and autism, please visit www.mitoaction.org and access the autism page at http://www.mitoaction.org/autism

Email your questions to:

Autism@...