Medical Testing for Autism, Asperger’s Syndrome, and PDD
By William Shaw, Ph.D.
It is generally accepted within the autism community – by parents and professionals alike – that autism is a behaviorally-based disorder, that is, diagnosis is based on observation of behavior and treatment focuses on alleviating challenging behaviors. However, a growing number of individuals within this expanding community also acknowledge that there exists an equally relevant biomedical component to the disorder that should not be overlooked in planning treatment programs for individuals with autism spectrum disorders. While recognizing the need for biomedical testing, both parents and medical professionals can be at a loss in understanding the array of tests available and how to determine which test(s) are most appropriate for a child or adult with an ASD.
The recommendations for testing that follow are based on my 10 years experience as a Laboratory Director of The Great Plains Laboratory, a medical laboratory which has performed more testing for people on the autism spectrum than any other place in the world. My recommendations are now also based on experience with my own 14-year-old stepdaughter, Paulina, who has severe autism.
Food Allergy Testing
The single most useful test for people on the autism spectrum is the comprehensive IgG food allergy test. The most common foods that are abnormal in children and adults on the spectrum are cow’s milk, cheese, yogurt, wheat, barley, rye, spelt, and soy. We have documented these allergies at The Great Plains Laboratory by testing thousands of blood samples from people on the spectrum throughout the world. Multiple articles in the medical journals report similar abnormalities.
The incidence of high IgG antibodies to wheat and milk is approximately 90% in people on the autistic spectrum. Most individuals with IgG allergy or sensitivity to cow’s milk are also allergic to goat’s milk. Other common allergies include peanuts, eggs, citrus fruit, corn, sugar, and baking yeast. There are various allergy tests available, so it is very important to check which type of allergy test is being offered. Although helpful in some cases, I have not seen IgE food allergy testing to be as valuable for individuals with ASD. Unfortunately, this is the only kind of food allergy test that most laboratories offer.
Determining whether or not IgG food allergies are present is important. These allergies or sensitivites are associated with the reaction of foods with certain white blood cells that release powerful cytokines, protein substances like gamma-interferon that can cause profound behavioral changes and even psychosis. IgG allergies are found in children and adults on the entire autistic spectrum including autism, pervasive developmental disorder (PDD), and in Asperger’s syndrome. These abnormalities are also very common in attention deficit disorder as well.
Wheat and milk restriction has been one of the most successful treatments for individuals on the spectrum. Prior to initiation of the gluten and casein free diet, Paulina spent most of the day screaming, crying, throwing tantrums and pulling things off the shelves. She could not go to dinner at a restaurant because she was so hyperactive that she would squirm out of her seat and wander around the restaurant. All of these difficult behaviors ceased after implementation of the gluten free and casein free diet (as well as an antifungal treatment).
Testing for Celiac Disease
Celiac disease is another common disorder of wheat intolerance with an incidence of about 1:150 among people of European descent. The incidence of this disorder does not appear to be higher in those on the autism spectrum than in the general population, although people on the spectrum occasionally have celiac disease also. Celiac disease can be confirmed by the presence of antibodies to the intestinal enzyme transglutaminase, which is involved in the biochemical processing of gluten.
Inhalant Allergy Testing
Allergies to things in the air is termed inhalant allergies. These allergies, in contrast to food allergies, do need to be tested with IgE tests. Some of the most common allergies are mold, mildew, pollen, cats, dogs, birds, and dust. One child with autism had a severe behavioral reaction whenever a certain special teacher entered the classroom. After testing for inhalant allergies, we found that the child had severe cat allergies. The teacher was a cat lover and had several at home. The cat hair would get on the teacher’s clothes and trigger allergic reactions in the child. The child was transferred to another teacher and the severe behavioral reactions ceased.
Testing for Yeast
Another very common abnormality in autism is a gastrointestinal overgrowth of Candida. Candida is a member of the yeast family – a type of fungus. Drugs that kill yeast or fungus are called antifungal drugs. The greatest bulk of Candida is present in the intestinal tract, although it may occasionally enter the bloodstream and has been detected in the blood of children with autism by a highly sensitive test called PCR that measures the Candida DNA. There are about a dozen species of Candida but three of the most common are Candida albicans, Candida parapsilosis, and Candida krusei.
There are many reasons for controlling Candida overgrowth. Excessive Candida can inhibit normal digestion and absorption of nutrients into the bloodstream, as well as prevent the production of important vitamins needed for optimal health. Candida produces many toxic byproducts including gliotoxins, which can cause impairment to the immune system. In addition, large portions of a Candida cell wall protein (HWP1) have a structure which is virtually identical to the wheat protein gluten. Because of this similarity, Candida binds to the enzyme transglutaminase, which is present in the intestinal lining. This binding to transglutaminase anchors long strands of the yeast cells to the intestine like ivy vines climbing a brick wall. This anchoring inhibits the yeast from being mechanically dislodged as digested food passes by. The binding of Candida to transglutaminase also interferes with the normal function of this enzyme in the digestion of gluten. If pieces of the Candida cell wall protein (which is similar to gluten) enter the bloodstream, they may react with one of the blood clotting factors that also has transglutaminase activity, leading to interference in the blood clotting mechanism. These modified proteins may not be recognized by the immune system, which as a result, can lead to autoimmune diseases. Lastly, the Candida cells can also produce digestive enzymes like proteases and phospholipase that actually eat away the intestinal lining, allowing undigested food molecules to pass through into the bloodstream, and as a result, cause more food allergies.
Candida can be detected by culturing the stool on Petri dishes or by measuring the amount of chemicals produced in the intestinal tract. These byproducts can be measured in the urine organic acid test (OAT), which also checks for inborn errors of metabolism, nutritional deficiencies, and other factors. These chemicals or fermentation products are absorbed from the intestinal tract by the blood vessels called the portal veins. These blood vessels carry these fermentation products to the liver where they are distributed throughout the bloodstream. The blood containing these fermentation products is filtered through the kidney and is excreted in the urine.
It is important to know that Stool testing can frequently miss the presence of Candida when there are high amounts of antibodies called IgA in the intestine. These IgA antibodies may coat the yeast cells and inhibit their growth enough to prevent them from growing in the Petri dish even though they may still be able to grow enough in the intestine to cause problems. Such a situation can lead to a false negative result.
By testing the yeast fermentation products in urine, this problem can usually be overcome. However, about 10% of yeast do not produce the common fermentation products. We have resolved this problem by offering a COMBO test for both the yeast fermentation products – the urine organic acid test (OAT) – as well as the yeast culture from stool. If the yeast can be cultured, there is the added advantage that the sensitivity of the yeast to various drugs or natural agents can be determined. Many yeast have developed resistance to various antifungal drugs because of the widespread use of these drugs in people with human immunodeficiency virus (HIV) infection. Like people with HIV, many people on the autism spectrum have a serious lack of immunity to Candida. One possible reason that people with autism have this problem is that the measles vaccine virus can severely impair the ability of the cellular immune system (Vaccine Jan 8, 2001) to control Candida. We have found this same lack of cellular immunity in people with autism. The Great Plains Laboratory expects to have a test for this defect available shortly and a possible treatment as well.
Alongside the GF/CF diet, reducing or eliminating yeast overgrowth has been one of the more effective methods of reducing autistic symptoms. Paulina had been on antifungal treatment (Nystatin) for several years but her behavior began to deteriorate markedly. Testing showed that her yeast had developed resistance to Nystatin. With this change, she had become extremely hyperactive and uncooperative. She spent much of the time crying and whining, had difficulty sleeping, and pulled things off the table. Within six hours of starting the antifungal drug Diflucan, her normal smiling behavior returned. Unfortunately, with prolonged use, Diflucan can sometimes cause liver damage so we implemented a limited carbohydrate diet to help control the yeast after we discontinued the Diflucan. With successful antifungal treatment, parents have reported reduced aggressive and self-hurtful behaviors, improved learning at school, improved focus and concentration, better sleep and reduced hyperactivity. Many parents don’t realize that antifungal treatment is a long-term issue in autism; others treat with antifungal drugs that are ineffective. It’s important that antifungal treatment be done under the supervision of a qualified medical professional. A less expensive microbial organic acid test can be done regularly to make sure that the yeast or harmful bacteria have not returned.
Testing for Clostridia
Several years ago, I began a collaborative study with Dr. Walter Gattaz, a research psychiatrist at the Central Mental Health Institute of Germany in Mannheim to evaluate urine samples of patients with schizophrenia. These samples were very valuable since they were obtained from patients who were drug-free. Thus, any biochemical abnormalities would be due to their disease and not a drug effect. Five of the twelve samples contained a very high concentration of a compound identified as a derivative of the amino acid tyrosine, which is very similar to but not identical to 3,4-dihydroxyphenylpropionic acid. I have since identified this compound as 3-(3-hydroxyphenyl)-3-hydroxypropionic acid or HPHPA. This particular compound has been linked to colonization of the intestinal tract with Clostridia bacteria.
How is this important to autism? HPHPA is found to be much higher in the urine of autistic children than in normal children. People with autism who have high values of this compound may have extremely abnormal or even psychotic behavior. One child with high amounts of HPHPA in urine kicked out the windows of the family car while being transported to school. Clostridia can be treated with the antibiotics Vancomycin or Flagyl. The first patient in a medical study improved after Flagyl treatment but then regressed when the drug was discontinued. The same child was retreated with a six-week course of Vancomycin. A developmental specialist estimated that the child had gained six months of development after the six weeks of therapy. Again, the child regressed after discontinuation of therapy. The use of beneficial bacteria, Lactobacillus acidophilus GG, whose brand name is Culturelle, is very useful in controlling Clostridia species in most cases and can be safely used for years if necessary. This product has about a millionth of a gram of the milk protein casein in each capsule but such a small amount is unlikely to have a significant effect in most milk-sensitive people.
Testing for HPHPA is also included on the full organic acid test or microbial organic acid test of the Great Plains Laboratory. It is important to be aware that some laboratories incorrectly measure DHPPA as a marker for Clostridia.DHPPA is a byproduct of chlorogenic acid, a common substance found in beverages and in many fruits and vegetables including apples, pears, tea, coffee, sunflower seeds, carrots, blueberries, cherries, potatoes, tomatoes, eggplant, sweet potatoes, and peaches. In addition, it is also a chemical byproduct of the good bacteria, E-coli and Lactobacillus.
The Toxicity of Mercury
Mercury is a naturally occurring metal found throughout the environment. Mercury can enter the environment from deposits of ore containing mercury due to wind or rain or from the actions of humans. In addition to mercury from the vaccine preservative Thimerisol, other major sources of mercury that contaminate humans are dental fillings, which are about 50% mercury and large fish such as tuna and swordfish.
Mercury exists in two major forms, inorganic and organic. Inorganic mercury consists of metallic mercury and inorganic mercury compounds called salts. Metallic mercury is a liquid at room temperature. It is the shiny silver material in thermometers and is commonly combined with silver as an alloy for dental fillings. Liquid mercury from thermometers can give off vapor if a thermometer breaks which could then be absorbed through the lungs. Mercury is also used in alkaline batteries. Organic mercury compounds include methylmercury, ethylmercury, and phenylmercury. Methylmercury is produced from inorganic mercury by microorganisms in the environment and perhaps by the microorganisms in the intestinal tract. Methylmercury is extremely toxic. Exposure to three drops of methylmercury to the gloved hands of a researcher was fatal. Mercury exposure should be avoided at all costs.
It is important to note that the symptoms of mercury toxicity closely mirror the clinical symptoms of autism.. Parents of a child who had developmental delays and a muscle disorder contacted me because the child’s tests had revealed high levels of mercury in the hair and blood. They reported that their child ate salmon or tuna five or six times a week. Although fish are an excellent source of essential fatty acids, most large fish have significant amounts of methylmercury. The FDA has recommended that pregnant women abstain from certain fish high in mercury. Since methylmercury is fat soluble, it might also contaminate supplements derived from fish oils. In addition, mercury was used as an antifungal agent in paint prior to 1992. Therefore, anyone in an older house needs to be aware that peeling paint or sanding off existing paint could lead to mercury exposure. Mercury in the fillings of pregnant women may be a significant source of exposure to developing infants in utero. Ethyl mercury, the most common preservative found in vaccines, has been present as a preservative in other products as well: contact lens solutions, nasal sprays, and in ear and eye drops.
Testing for Heavy Metals
Heavy metals may often have combined effects so that exposure to multiple heavy metals at low levels might be just as toxic as exposure to one metal at a high level. Heavy metals found to be elevated in children and adults with autism and PDD include uranium, mercury, cadmium, arsenic, lead, aluminum, and antimony. Hair is the easiest sample to collect in most cases and is generally considered one of the best samples for screening for heavy metals since the heavy metals, such as mercury, may be 250 times higher in the hair than in the blood. However, the use of hair metal testing is controversial. The State of New York bans hair testing for heavy metals while the Environmental Protection Agency (EPA) of the US Government promotes hair screening for mercury as a very useful method. In New York State tests for heavy metals in blood or urine may have to be used instead of hair. Chelation treatment with the chelating agent DMSA is probably the most effective treatment at this time for those people with abnormal values.
Multiple tests can be very useful to pinpoint the most significant biochemical abnormalities so that treatment can be focused on the most important issues. Although each autistic child will experience varying levels of success with biomedical testing and treatments, I would like to share one success story that outlines what can happen in some cases. Three years ago, a family came to visit from Turkey with their four-year-old son with severe autism. They insisted that they wanted every single test offered by the laboratory. I tried to convince them to reduce the financial burden by suggesting which tests might be delayed to a later time. They would not listen and insisted firmly that they get every test available. Two years later I received a letter from the parents who had implemented all the therapies indicated by the testing. Their son had completely recovered and was successfully attending a regular school classroom without an aide.
The tests emphasized in this article have been useful to people with autism of every degree of severity. Parents and treating professionals who want to embark on biomedical testing should first start with this group. Many other tests may be useful to people with autism of every age; they are indicated in Table 1. Most tests are covered by insurance but HMO’s generally do not pay unless the physician gets advance approval from a review committee.
As concerned parents and professionals, it is vitally important that we be holistic in our approach to treatment and investigate whether or not biomedical/biochemical agents are contributing to autistic symptoms. Only then will we be best able to successfully reduce or eliminate the behavioral challenges associated with autism spectrum disorders.
William Shaw Ph.D. is the Director of The Great Plains Laboratory, Inc., which specializes in metabolic and nutritional testing, especially in autism. Dr. Shaw received a Ph.D. in biochemistry, genetics, and human physiology from the Medical University of South Carolina and is board certified in the fields of clinical chemistry and toxicology by the American Board of Clinical Chemistry. He has supervised large endocrinology, nutritional biochemistry, toxicology, and immunology departments in positions at the Center for Disease Control and Smith Kline Clinical Laboratories in Atlanta, Georgia. He was Director of Clinical Chemistry, Endocrinology, and Toxicology at Children’s Mercy Hospital, the teaching hospital of the University of Missouri at Kansas City School of Medicine. For more information telephone 913.341.8949; email: GPL4U@aol.com; website: www.greatplainslaboratory.com.
This article is reprinted with permission from the July-August 2004 issue of the Autism Asperger’s Digest, a 52-page bimonthly magazine on autism spectrum disorders, published by Future Horizons, Inc. Subscribe at www.autismdigest.com.