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