Researchers are investigating whether some cases of autism are caused by defects in mitochondria – the energy factories inside the body’s cells.
Autism spectrum disorders are associated with social interaction problems, poor verbal and nonverbal communication, and repetitive behaviors. The disorders range from severe (autism) to mild (Asperger’s syndrome), and in total they affect about 1 in 110 American children.
The causes of autism spectrum disorders are unclear, but genetic factors are known to play a role. In recent studies, researchers have found that the risk of autism is affected by variation in several different genes involved in forming and maintaining the connections between nerve cells. Still, those genes do not tell the whole story. Across the autism spectrum – and even in a single individual with autism – it is likely that a number of genetic factors are at play.
Douglas C. Wallace, Ph.D., director of the Center of Mitochondrial and Epigenomic Medicine at the Children's Hospital of Philadelphia, theorizes that a significant number of autism spectrum disorders are linked to genes required by mitochondria. He is investigating that theory with a grant from the National Institute of Neurological Disorders and Stroke (NINDS), funded through the American Recovery and Reinvestment Act (ARRA).
Inside cells, mitochondria use oxygen and fuel derived from food to produce energy and support the body’s metabolism. More than 1500 genes are required for mitochondrial function; most of those genes reside within chromosomal DNA inside a cell’s nucleus (nDNA) and some reside within DNA inside the mitochondria themselves (mtDNA).
In the 1970s, Dr. Wallace demonstrated that mtDNA is passed exclusively from mother to child, pointing to mtDNA as the culprit in a number of disorders that follow a maternal inheritance pattern.
Mutations in nDNA or mtDNA can lead to a variety of syndromes that are known collectively as mitochondrial disorders. Symptoms vary, but often include developmental delays, learning disabilities and other neurological symptoms similar to autism.
There is also some evidence specifically linking autism to defective mitochondria. Small studies have found that some autistic children have metabolites in their blood that build up when mitochondria are not working properly. A small study of 20 children found that autistic children were more likely to have mtDNA abnormalities than were non-autistic children.
"A lot of data point toward mitochondrial involvement in autism. Our goal is to build on prior research and study a large patient population to look for mutations that affect mitochondrial function," said Dr. Wallace.
Dr. Wallace and his team will test blood samples from 200 patients with autism to scan for mutations in nDNA and mtDNA. If mutations are found, the team will use a number of techniques to confirm that the mutations interfere with mitochondrial function. This includes blood tests to check metabolites, plus a battery of non-invasive tests – such as an imaging technique and a breathalyzer technique – to look for abnormal metabolite levels in muscle and brain tissue.
The research may provide new approaches to diagnosing and treating autism spectrum disorders. Dr. Wallace's lab has experience generating mice that harbor nDNA and mtDNA mutations, and is prepared to use such mice to test potential therapies for autism.
"We could make significant inroads into treatment," he said.
- By Daniel Stimson, Ph.D.
Image caption: In these cultured cells, countless mitochondria (yellow) are moving toward the growing edges of the cells, where energy demands are high. Courtesy of Dr. Douglas Wallace, Children's Hospital of Philadelphia.
Last updated June 24, 2011