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.
BIO
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:
http://www.greatplainslaboratory.com.
The
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