Mitochondrial Disease and Autism
Date First Published: November 22, 2010
The possibility that there is a form of autism that co-occurs with, or is caused by, mitochondrial disease has recently come under intense discussion. How often might the two conditions occur together, and does autism associated with mitochondrial disease look different than typical autism?
What is Mitochondrial Disease?
Mitochondria are tiny structures found in nearly every cell in the body. Called the "power house" of the cell, they turn sugars, fats, and other nutrients into the energy cells require to function, and are responsible for producing 90% of the energy our bodies need.1,2 Mitochondrial disease occurs when the mitochondria are not working properly, causing cells to malfunction or die for lack of energy. The United Mitochondrial Disease Foundation compares this to what happens in a city undergoing a brown-out: “Imagine your body working with one-half of its energy-producing facilities shut down. The brain may be impaired, vision may be dim, muscles may twitch or may be too weak to allow you to walk or write, your heart may be weakened, and you may not be able to eat and digest your food.” 2
According to Dr. Richard Kelley, a researcher at the Kennedy Krieger Institute in Baltimore, Maryland, it is currently estimated that there may be as many as 1200 mitochondrial diseases. Fewer than 300 have been identified, however, and most of these are relatively severe disorders that have been the easiest to recognize.
Many of the known genetic mitochondrial disorders are progressive, affecting multiple systems, especially organs that have high energy demands such as the brain and nerves, the skeletal and cardiac muscles, and the liver and kidneys. Because the brain has the highest energy demand of any tissue, mitochondrial diseases cause a variety of neurological problems, including intellectual disability, seizures, developmental regression, gastrointestinal problems, and lack of coordination. In addition, because muscles also have a high demand for mitochondrial energy, low muscle tone, weakness, and fatigue are features of many mitochondrial diseases. Although a person has a mitochondrial disease from birth, certain stressors such as infections, fevers, dehydration, or a reduced intake of calories can cause acute worsening. 3
Mitochondrial Disease and Autism Spectrum Disorders
In recent years, it has been noted that that autism spectrum disorders (ASDs) and mitochondrial disease occur together more often than you would expect them to by chance. 4 For example, one population-based study of 120 children with ASD in Portugal found that 4.2% had biochemical evidence of mitochondrial disease. The researchers believed this was probably an underestimation, because only slightly more than half of the children in the study were even tested for this. 5 In a review of a number of studies looking at the issue, researcher Richard Haas stated: "There is convincing evidence for a mitochondrial role in a subset of children with ASD. Evidence of mitochondrial dysfunction is seen in at least 8% of ASD subjects and a number clearly have mitochondrial disease." 4 (Of course, this would also mean that more than 90% of children with ASD do not have mitochondrial disease.)
Overall, patients with ASD and biochemical evidence of mitochondrial dysfunction have relatively mild, non-progressive forms of mitochondrial disease compared to most of the known genetic causes of mitochondrial disease. This may be why the association of mitochondrial disease with ASD has taken so long to recognize.
As researchers continue to investigate, they are asking if children with ASD and mitochondrial disease have different symptoms or a different profile than children with typical ASD. So far, the answer appears to be “yes.” In one study of 25 children with both conditions, for example, fully 84% had major medical problems; 76% had “constitutional problems” (like becoming fatigued very easily); 40% had regressed in an unusual way; and 32% had a delay in achieving early gross motor milestones. None of these problems occur as frequently in children with typical ASD. 7 It should be noted that the criteria for patient inclusion in this study, as in the earlier Portuguese study, were stringent and would be expected to exclude milder forms of mitochondrial disease.
In one high profile case of mitochondrial disease and autism, it was suggested that vaccination may have triggered severe regression in a child who had an underlying but, until then, invisible mitochondrial disease. 7 In a study that looked at the records of 28 children with autism and mitochondrial disease, about 60% had experienced regression. More than two-thirds of this group regressed after a high fever, but not all of these fevers occurred after vaccination. These results led the researchers to conclude: “Although recommended vaccination schedules are appropriate in mitochondrial disease, fever management appears important for decreasing regression risk.” 8 Some researchers are now beginning to explore the possibility that it is inflammation, not fever itself that stresses a person with mitochondrial disease, causing regression. 4 If that were the case, then controlling inflammation, not fever, would be a key goal in the medical management of vulnerable individuals. (For example, a physician might recommend ibuprofen, which controls both fever and inflammation, rather than acetaminophen, which controls fever alone.)
Should Children with ASD be Tested for Mitochondrial Disease?
Tests for mitochondrial disease can be very involved, and include taking multiple samples of blood and even muscle, so such testing is not ordered routinely. In that case, which children should be tested for mitochondrial disease? Dr. Haas has suggested that children with ASD who have experienced a major or unusual regression, or who have symptoms of multisystem disorders (particularly GI dysfunction) are the most likely to also have mitochondrial disease. 4 In line with this, the Centers for Disease Control (CDC) is telling parents that doctors decide whether testing for mitochondrial diseases should be done based on a child's signs and symptoms. 1
It is important to note that research on mitochondrial disease and autism is just beginning; percentages of those affected, recommendations for testing or treatment, and our understanding may all change as we learn more. Interest in what some are calling Mitochondrial Autism is growing, and experts from both fields have begun to convene joint meetings and collaborate. 3,9