This week’s “Got Questions?” answer comes from Deepa Menon, MD, assistant medical director of the Center for Autism and Related Disorders, at Baltimore’s Kennedy Krieger Institute—an Autism Speaks Autism Treatment Network (ATN) site. Her research interests include metabolic and mitochondrial disorders and their association with autism.
Mitochondria are cell structures, or “organelles,” whose primary function is to supply a cell with energy. In essence, they turn sugar and fatty acids from food into the energy-carrying molecule adenosine triphosphate (ATP).
Virtually every cell in the body depends on ATP and mitochondria for energy. As a result, mitochondrial disorders can produce a wide variety of symptoms. The most common involve body systems that use a lot of energy. Muscles are a classic example, and mitochondrial dysfunction often produces muscle weakness and fatigue. When mitochondrial dysfunction affects the gastrointestinal system, symptoms can include constipation or diarrhea. When it affects the immune system, it can lead to frequent infections. Mitochondrial disorders can likewise cause failure to grow, kidney dysfunction and a many other medical problems.
The brain is another energy-demanding system. Here, mitochondrial dysfunction can produce such symptoms as developmental delay, hearing problems and seizures.
Over the last decade, there has been great interest in the possibility that mitochondrial disorders may underlie some of the symptoms of autism spectrum disorder (ASD). Currently we believe that around 5 to 10 percent of children with autism have mitochondrial dysfunction as the underlying cause of their symptoms.
Research suggests that many children diagnosed with autism and underlying mitochondrial dysfunction experienced regression following a simple childhood illness (ear infection, common cold, etc.) or other cause of fever or inflammation. Regression refers to a loss of developmental skills such as language or motor abilities. It may be accompanied by other symptoms of mitochondrial disorder such as fatigue, gastrointestinal distress, seizures and/or motor delays.
Laboratory testing of blood samples and urine show that many of these children (with ASD and mitochondrial dysfunction) have abnormally high levels of certain amino acids and cellular waste products. This suggests that their cells are generating energy inefficiently with an excess of damaging byproducts.
When a child is diagnosed with ASD and mitochondrial dysfunction, treatment goals include a bolstering mitochondrial activity and protecting the mitochondria from further damage. Parents and affected individuals may be counseled to avoid (as much as possible) situations that stress mitochondria. Examples of these stresses include going for long periods between meals (prolonged fasting), infections that produce fevers, inflammation associated with dietary sensitivities and certain medications such as the antipsychotic haloperidol (Haldol), which is known to impair mitochondrial function.
Supportive treatment can include a prescription nutrient mixture containing the protein L-carnitine and the B-vitamin pantothenate, which is thought to bolster mitochondrial activity. This prescription mixture usually contains additional nutrients such as thiamine, nicotinamide, lipoic acid, and vitamins C and E. Coenzyme Q10 may be added for those who show low levels of CoQ10 on testing.
[Editor’s note: Autism Speaks continues to support research into the association of mitochondrial disease and autism and their effective treatments. For more information on these and other funded studies, please explore our Grant Search portal, here.]
Development of language and social skills in children with autism differs from children with typical development and children with non-autism language delays (see Autism Speaks Top 10 Research Achievements of 2009; Pickles et al., 2009;). And different children with autism show different patterns of development. For some children, signs of autism appear very early, sometimes in the first year of life. In other children with autism, development does not strike parents as too unusual, with milestones such as walking and saying first words appearing generally on time. But then the child’s patterns of behavior begin to change. The nature of this change may differ from child to child. Some children stop saying words. Others become more socially withdrawn, less often directing social smiles toward others and less frequently trying to initiate social interactions. Children showing this pattern of development are said to have had a regression. The regression can occur rapidly over a period of weeks or slowly over a period of months.
Most of what is known about regression comes from historical accounts such as a review of medical charts, with researchers looking for early parental report or physician observation of a loss of skills. Another type of historical account involves interviewing parents of children with autism about whether their child lost skills. Most such studies have focused on language regression, where parents were asked whether their child had begun to talk and then lost their spoken language skills. That research indicated that about a third of children with autism ‘regressed’, and that the regression usually occurred between the first and second birthday.
More recently, researchers have begun to study development of autism beginning in infancy, prior to the clear behavioral manifestation of autism, and continuing through the third birthday, the age at which autism is commonly diagnosed. One approach is to study development of infant siblings of children with autism; this group of children is at increased risk for autism and a range of milder impairments. Research conducted by my colleagues and I, which uses this type of approach, is helping to clarify questions about regression, as you will see from the description of our findings below. All of the infants who develop autism in these studies have an older sibling with an autism spectrum disorder (ASD). Thus, these findings may apply only to children who are from families who have more than child with autism. Other patterns of development and regression may occur in other forms of ASD.
We have found that high risk infants who later receive a diagnosis of autism show few, if any, signs of abnormal development at 6 months of age. If present, the signs of a developmental problem may be very subtle, sometimes involving aspects of development that are not considered to be core deficits of autism. For example, the signs may involve fine motor delays, which are not specific to autism. But by the time of the first or second birthday, development is not unfolding as expected.
By 14 months of age, half of the children with a later diagnosis of autism show enough symptoms of autism to be diagnosed by an expert. Other children with autism do not show enough symptoms to be diagnosed until later, like 2 or 3 years of age. Nevertheless, most, if not all, of these children show some type of delay in development near the time of the first birthday. For more details, please see two papers: Landa & Garrett-Mayer, Journal of Child Psychology and Psychiatry, 2006; and Landa, Holman, & Garrett-Mayer, Archives of General Psychiatry, 2007.
Thus, there appear to be two major patterns of onset of autism in these high risk infants: (1) a pattern where clear symptoms of autism are present near the time of the first birthday; and (2) later manifestation of autism symptoms, but with subtle to moderate delays (usually in language and/or social development) already present near the time of the first birthday. For both groups, the rate of development of new skills gradually slows down during the first two years of life, meaning that the children are not keeping up with their typically developing peers. A loss of skills, decline in the frequency of social initiation, decrease in the variety of speech sounds or gestures produced communicatively, decrease in variety and quality of play, and so forth may be superimposed on the slowing in rate of development. These patterns of development may be considered a form of regression.
This new information about development in children with autism suggests that autism may be considered a “progressive disorder”, with regression being an extreme form of the progressive worsening. Sudden and severe loss of existing skills, with previously perfectly typical development appears to be a rare event in children with ASD who have more than one child with ASD in the family. More commonly, the worsening is so gradual that parents do not report that their child actually ‘regressed’ or lost skills, even in children whose test results show a decline in development over time.
Our research findings have several important implications for families and health care providers. Screening for general development should be a standard practice, occurring by 9 months and being repeated through the third birthday (e.g., 18, 24, 36 months). The American Academy of Pediatrics also recommends that all children be screened for autism at 18 and 24 months of age. If a parent becomes concerned that a child’s pattern of development has changed for the worse, or that signs of autism are emerging, screening or referral for more in-depth assessment should occur. Early detection of autism enables families to enroll their children in intervention earlier in life, and hopefully improve their child’s outcome. Families with concerns about their child may also seek free assessments and intervention from their local public Infants and Toddlers program.
Bhat A, Rusyniak J, Landa R. (2007). Motor and cognitive development of infants at risk for autism and low risk typically developing infants. International Meeting for Autism Research, Seattle, WA.
Bhat A, Galloway C, Landa RJ. Social and Non-social Visual Attention Patterns and Associative Learning in Infants at risk for Autism. Journal of Child Psychology and Psychiatry. In press.
Landa R, Garrett-Mayer E. (2006). Development in infants with autism spectrum disorders: A prospective study. Journal of Child Psychology and Psychiatry. 47(6):629-638.
Landa RJ, Holman KC, Garrett-Mayer E. (2007). Social and communication development in toddlers with early and later diagnosis of autism spectrum disorders. Archives of General Psychiatry. 64,853-864.
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