The cause of autism may be faulty mitochondria December 3rd, 2010

AUTISM is a puzzling phenomenon. in its pure form it is an inability to understand the emotional responses of others that is seen in people of otherwise normal—sometimes above normal—intelligence. however, it is often associated with other problems, and can also appear in mild and severe forms. This variability has led many people to think of it as a spectrum of symptoms rather than a single, clear-cut syndrome. and that variability makes it hard to work out what causes it.

There is evidence of genetic influence, but no clear pattern of inheritance. The thought that the underlying cause may be hereditary, though, is one reason for disbelieving the hypothesis, which gained traction a few years ago but is now discredited, that measles vaccinations cause autism.

One suggestion that does pop up from time to time is that the process which leads to autism involves faulty mitochondria. The mitochondria are a cell’s powerpacks. They disassemble sugar molecules and turn the energy thus liberated into a form that biochemical machinery can use. Mitochondrial faults could be caused by broken genes, by environmental effects, or by a combination of the two.

Nerve cells have a huge demand for energy, so a failure of the mitochondria would certainly affect them. The question is, could it cause autism? to try to find out Cecilia Giulivi of the University of California, Davis, and her colleagues studied the mitochondria of ten children, aged between two and five years, who had been diagnosed with autism. They have just published their results in the Journal of the American Medical Association.

Extracting nerve cells from the brains of children for a study like this is obviously out of the question. Instead, Dr Giulivi used immune-system cells called lymphocytes as surrogates. Lymphocytes, like nerve cells, use a lot of energy and thus rely heavily on their mitochondria. They are also easy to extract from blood. Dr Giulivi and her colleagues did just that, and then examined the activity of the lymphocytes’ mitochondria.

The children in question were randomly selected from a previous study on autism. They were matched with ten children of similar ages and ethnic backgrounds who were developing normally. Dr Giulivi found that mitochondria from children with autism consumed far less oxygen than those from the control group. that is a sign of lower activity. one important set of enzymes—NADH oxidases—used, on average, only a third as much oxygen in autistic children as they did in non-autists, and eight of the autistic children had significantly lower NADH-oxidase activity than is normal.

The mitochondria of the autistic children also leaked damaging oxygen-rich chemicals such as hydrogen peroxide. These are a normal by-product of mitochondrial activity, but are usually mopped up by special enzymes before they can escape and cause harm—for instance, by damaging a cell’s DNA. The level of hydrogen peroxide in the cells of autistic children was twice that found in non-autists. such high levels suggest the brains of autistic children are exposed to a lot of oxidative stress, something that would probably cause cumulative damage.

These results need to be taken with caution. First, ten is an extremely small sample. second, on the face of things, mitochondrial diseases appear far rarer than autism. They are diagnosed in fewer than six per 100,000 people in America, while autism of some sort is seen in as many as one in 110. Moreover, previous attempts to show a link have come up with a much weaker correlation between the two phenomena. a study of 69 autistic children that was published in 2005 found mitochondrial abnormalities in only five of them. that is higher than the background rate of mitochondrial disease, but nevertheless suggests that faulty mitochondria are not the only cause of autistic symptoms. This study did, however, use a broader sample of the autistic spectrum than Dr Giulivi’s, and looked at muscle cells, whose metabolic profiles are very different from nerve cells and lymphocytes.

It is also important to remember, in studies like this, that correlation is not causation. some third effect could be triggering both the symptoms of autism and the mitochondrial dysfunction. if it is really the mitochondria that are causing the problem, though, there is another hypothesis that needs to be addressed. This is that external triggers might expose such mitochondrial weaknesses earlier than would otherwise be the case.

In 2008 an American court awarded damages to a child after she developed health problems following routine childhood vaccinations. America’s Department of Health and Human Services looked into the child’s medical history and concluded that vaccines had significantly aggravated an underlying inherited mitochondrial disorder that predisposed her to metabolic problems that caused brain damage with features of autism.

The genetic condition in this particular case is rare: only four other examples are known. and no scientist—least of all Dr Giulivi—is suggesting that the new study bears on the question of environmental triggers of mitochondrial malfunction. But if faulty mitochondria do turn out to be a cause of autism, even if not in all cases, that question will have to be investigated. and you can bet your bottom dollar that somewhere out there is a lawyer wondering whether he can do just that.

Source: economist.com/node/17626864?story_id=17626864&fsrc=rss

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