Article Written by Amy S. Holmes, M.D.
Maintained and Hosted by The Healing Center On-Line
Reprinted with the kind permission of the author and William Walsh, Ph.D. -
Co-Founder and Senior Scientist - the Health Research Institute and Pfeiffer Treatment Center
email this page to a friend
You may also return to these areas:
[Color codes: blue = accessible page; light grey = page you are on; dark grey = in progress]
Metal-Metabolism and Autism
Introduction: Defective Functioning of Metallothionein Protein (MT)
Dr. William Walsh and Dr. Anjum Usman have discovered that defective functioning of metallothionein protein (MT) is a distinctive feature of autism. This abnormality results in impaired brain development and extreme sensitivity to toxic metals and other environmental substances. This disorder is often unnoticed in infancy and early childhood until aggravated by a serious environmental insult.
In a study of 503 autism-spectrum patients, the authors found abnormal levels of copper and zinc in blood (p<0.0001) indicating defective functioning of metallothionein (mt) proteins. also, calculation of unbound copper provides a reliable indication of the degree of metallothionein function (or dysfunction). in humans, mt proteins regulate blood levels of these trace minerals, detoxify mercury and other heavy metals, and assist in neuronal development. the expected consequences of defective mt during gestation or early infancy are consistent with several classic symptoms of autism. it appears that defective functioning of mt proteins may represent the underlying cause of autism.
It is very interesting to examine the consequences of MT malfunction in a newborn:
Consequences of MT Malfunction in a Newborn
Since the above factors closely resemble classic symptoms of autism, it is logical to conclude that the root cause of autism may be an error of metal-metabolism involving MT followed by victimization by a toxic metal.
- Abnormal Cu (Copper) and Zn (Zinc) levels in blood and in hippocampus
Impaired neuronal development, especially in the first 30 months of life, which could result in incomplete maturation of the G.I. tract and brain.
- Loss of MT's protective detoxification of heavy metals
MT is the primary system for managing cadmium, mercury, and other toxic metals. MT has an extraordinary affinity for these heavy metals and the resultant proteins (cadmium MT, mercury MT, etc.) effectively sequester the toxic metals and render them relatively innocuous.
- Impaired immune function
- Immature GI tract
The most likely explanation for the severe metal-metabolism dysfunction lies in the function of a group of proteins known as metallothioneins. Genetic errors in the genes coding for the various proteins or having the genes "turned off" by influences on the promoter regions on either side of the genes themselves would be the only two explanations for dysfunction of this group of proteins.
PCR (Polymerase Chain Reaction) studies of the genes coding for the various metallothionein proteins in autistic spectrum disorders have been negative (Segal, et al, accepted for publication). This means there is nothing wrong with these genes themselves, but the production of metallothionein proteins has somehow been "turned off" by other genetic and possibly environmental factors. Thus, by using items known already found in the medical literature to stimulate the production of metallothionein proteins, it should be possible to restore function to this entire system of proteins, thus allowing the restoration of function of these proteins. This should allow the body to naturally rid itself of accumulated heavy metals, help the GI tract to mature, and correct the immune system impairments.
Stimulating the Production of Metallothionein Proteins
With defective MT proteins, a fetus or infant is not able to efficiently excrete heavy metals to which he/she has been exposed. These heavy metals, if not excreted, lead to problems with heavy metal toxicity. If the fetus/infant receives no mercury exposure, even with severely compromised MT function, no problems result. At low mercury exposure rates, only those with the most severely compromised MT function are adversely affected. But, with higher and higher amounts of early mercury exposure, those with less severely dysfunctional MT systems will be adversely affected.
This is exactly what has been observed over the past 10 to 15 years. In the 1950's infants received 25 to 50 mcg mercury via vaccinations. The autism rate in the 1950's was about 2 in 10,000. The addition of another DPT vaccine in early infanthood became commonplace in the 1970's, and a small rise in the autism incidence rate was noted. In 1988, infants began receiving a Hib vaccination at 2,4, and 6 months, each vaccine containing 25 mcg of mercury. Then, in 1991, the hepatitis B vaccine was "mandated", with the first vaccination given within a few days of birth and 2 additional vaccines given during the 1st 6 months of life. Each hepatitis B vaccine contained 12.5 mcg Hg.
What Has Been Observed: Vaccinations, Mercury & Autism
Also, over the past 10 to 15 years, the practice of giving RhoGAM injections to Rh-negative women has undergone a dramatic change. In the early 1980's an Rh-negative woman meeting the criteria for RhoGAM administration received the injection immediately after birth of the child. The current recommendations now include routine administration of RhoGAM (in women meeting the criteria) at 28 weeks gestation, after amniocentesis, and (with some obstetricians) if any spotting occurs during pregnancy. The amounts of mercury contained in RhoGAM injections vary with the manufacturer, but most contain about 25 mcg Hg. Thimerosal-free RhoGAM injections are now available.
The current autism incidence rate is now 1 in 150 children. Even those epidemiologists who contended that the rise is simply due to better diagnosis have conceded that the increase is indeed real and is quite alarming (IMFAR Conference, 2001, San Diego).
Click here to see a chart showing the cumulative mercury exposure received during infanthood by birth year (weighted by compliance rates) and the DSM-IV autism incidence rate in California (the only state in which each child suspected of having a developmental delay must be evaluated by a central agency with unchanged criteria over the last 10 years). Note that the incidence rates reflect only full-fledged DSM-IV autism and not lesser diagnoses such as PDD/NOS.
MT is directly involved in neuronal development and maturation of the brain and G.I. tract, and the timing of environmental insults are critically important. By age three, these systems may have sufficiently matured so that environmental toxins can no longer provoke autism.
MT and Neuronal Development: Maturation of the Brain & the Timing of Environmental Insults
There are four primary types of MT protein: MT-I and MT-II are found in cells throughout the body, with MT-Ill restricted primarily to the brain and MT-IV to squamous epithelial cells in the intestines. The roles of the various MT proteins and isoforms are not well understood and are the subject of intensive research.
MT functioning involves (1) induction of thionein, (2) "pre-loading" with Zn atoms, and (3) redox reactions in which Zn may be displaced by other metals. MT proteins are induced by Zn, Cu, Cd, and other toxic and nutrient metals. In addition, MT can be induced by injury, emotional stress, and/or nuclear radiation and is an important anti-oxidant system in the body. A primary mechanism for Zn loading and metal binding is the glutathione (GSH), glutathione disulfide (GSSH) redox couple.
There is now evidence that autism can be caused by a biochemical abnormality, which disables MT protein accompanied by early exposure to neurotoxins such as mercury. Mechanisms with the potential for disrupting MT functioning include severe Zn depletion, impaired synthesis of GSH, toxic metal overload, a pyrrole disorder, and a sulfur amino acid abnormality, along with a myriad of other genetic and/or environmental insults.
Evidence that Autism Can Be Caused by Early Exposure to Neurotoxins Such As Mercury
The discovery of disordered metal-metabolism in autism may lead to early identification of autism-prone children, prevention of regressive autism, and improved therapy outcomes.
Also, the ongoing elimination of thimerosal from infant vaccines (as recommended by both the FDA and AAP starting in 1999) and from RhoGAM injections (a more recent development) should result in much lower autism incidence rates in the coming years. We should start noticing the decline in 2 to 3 years as the children born in 2000-2001 approach the ages at which autism is most commonly diagnosed.
The new therapies aimed at elimination of existing heavy metals and the induction of the production of metallothionein should help the children currently affected, dependent on age at the initiation of therapy in those children found to have dysfunctional MT systems.
Amy S. Holmes, M.D.
March 5, 2002
[Return to "Quick-Index" for Metal-Metabolism and Autism]
[Return to "Quick-Index" for Metal-Metabolism and Autism]
You may also return to these sections: