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Metal-Metabolism and Autism


Pfeiffer Treatment Center http://www.hriptc.org/

Presented by William Walsh, Ph.D. and Anjum Usman, M.D. at the American Psychiatric Association Annual Meeting, May 10, 2001 in New Orleans.

http://www.hriptc.org/MetalMetabolism_and_Autism.htm

The Pfeiffer Treatment Center (PTC) has discovered that defective functioning of metallothionein protein (MT) is a distinctive feature of autism. This abnormality (believed to be genetic) 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, PTC found abnormal levels of copper and zinc in blood (p<0.0001) indicating defective functioning of metallothionein (MT) proteins. In humans, MT proteins regulate blood levels of these metals, 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 a primary cause of autism.

MT is directly involved in neuronal development and maturation of the brain and G.I. tract, and the timing of environmental insults is critically important. By age three, these systems may have sufficiently matured so that environmental toxins can no longer provoke autism.

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 evidence that autism can be caused by either (a) a genetic MT defect or (b) a biochemical abnormality which disables MT protein. 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.

Definition of the ideal treatment of refractory autism may await definition of the specific genetic MT (or other) defect present. A defect of MT-I or MT-II would suggest a therapy concentrating on achieving homeostasis of metals in blood. A MT-III defect might indicate the need for regulation of glutamate chemistry in the brain. A MT-IV defect would suggest a focus on restoring proper G.T. tract function.

Metal-metabolism abnormalities observed in ADHD, behavior disorders, and mental illness may result from biochemical imbalances which impair MT functioning, rather than a direct genetic MT defect. This may explain the striking differences in autism patient outcomes. It is very likely that autistics with genetically-defective MT are more refractory to treatment than autistics with more readily correctable biochemical imbalances. The many documented cases of autism “reversal” may be restricted to patients with the latter type of MT disorder.

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. For example, PTC recently developed an advanced autism therapy aimed at promotion of normal MT functioning.


APA: New Research Suggests Cause of Autism

http://www.docguide.com/news/content.nsf/news/CFDE7A250AC2A

NEW ORLEANS, LA -- May 10, 2001 -- Autism, a poorly understood genetic disorder present in more than a half million Americans, may be caused by a defect in metal metabolism that impairs the development of the brain and can result in hypersensitivity to toxic environmental substances. In a study of 503 autism patients, 99 percent exhibited evidence of this metabolic disorder, according to information presented here today at the annual meeting of the American Psychiatric Association (APA).

Blood and urine analyses yielded evidence of a metallothionein (MT) dysfunction in 499 of 503 patients (99 percent) diagnosed with autism spectrum disorders, according to William J. Walsh, Ph.D., biochemist and chief scientist of the Pfeiffer Center, Naperville, Illinois, and Anjum Usman, M.D., a physician at the Center, who presented the findings in a presentation at the APA meeting.

"MT is a family of proteins essential for many important processes in the body, and a dysfunction in this system can explain most of the classic symptoms observed in autism," said Dr. Walsh. "An MT disorder may affect the development of brain neurons and may cause impairments in the immune system and gastrointestinal tract, along with hypersensitivity to toxic metals," he said.

The study included a search for distinctive chemical markers for the major components of autism spectrum conditions, including classic autism, Asperger's Disorder and pervasive development disorder with autistic features. No substantive differences were found among these populations. However all three populations exhibited a very high incidence of a severe metal-metabolism disorder.

"A careful analysis indicated that all but four of the 503 autism-spectrum subjects exhibited evidence of a metal metabolism disorder associated with MT functioning," Dr. Walsh said. The study findings suggest that the primary cause of autism may be an inborn error in MT functioning, perhaps aggravated by an environmental insult, he said.

The study findings also suggest that autism may be caused by either a genetic MT defect or a biochemical abnormality, which disables MT protein. If correct, the study finding could lead to an early infant screening test for autism predisposition, and advanced treatments to correct the metal-metabolism disorders.

SOURCE: Pfeiffer Treatment Center

Additional Reading

Metal-Metabolism and Human Functioning, by William J. Walsh, Pfeiffer Treatment Center http://www.hriptc.org/mhfres.htm

 

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