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$Unique_ID{BRK04333}
$Pretitle{}
$Title{Wilson's Disease}
$Subject{Wilson's Disease Hepatolenticular Degeneration Lenticular
Degeneration, Progressive Chorea, Sydenham's Cirrhosis, Primary Biliary Heavy
Metal Poisoning Levine-Critchley Syndrome Huntington's Disease Tourette
Syndrome Cerebral Palsy }
$Volume{}
$Log{}

Copyright (C) 1985, 1986, 1990, 1991, 1992 National Organization for Rare
Disorders, Inc.

26:
Wilson's Disease

** IMPORTANT **
It is possible that the main title of the article (Wilson 's Disease) is
not the name you expected.  Please check the SYNONYMS listing to find the
alternate name and disorder subdivisions covered by this article.

Synonyms

     Hepatolenticular Degeneration
     Lenticular Degeneration, Progressive

Information on the following diseases can be found in the Related
Disorders section of this report:

     Chorea, Sydenham's
     Cirrhosis, Primary Biliary
     Heavy Metal Poisoning
     Levine-Critchley Syndrome
     Huntington's Disease
     Tourette Syndrome
     Cerebral Palsy

General Discussion

** REMINDER **
The Information contained in the Rare Disease Database is provided for
educational purposes only.  It should not be used for diagnostic or treatment
purposes.  If you wish to obtain more information about this disorder, please
contact your personal physician and/or the agencies listed in the "Resources"
section of this report.


Wilson's Disease is a rare genetic disorder characterized by excess
copper stored in various body tissues, particularly the liver, brain, and
corneas of the eyes.  Later developments include liver (hepatic) disease and
central nervous system dysfunction.  Early diagnosis and treatment may
prevent serious long-term disability.

Symptoms

Wilson's Disease usually begins with hepatic (liver) or neurologic
disturbances, or both.  Symptoms of liver dysfunction usually appear after 6
years of age.  Jaundice causes a yellow discoloration of the skin, mucous
membranes and the sclera of the eyes (membranes that line the eye).  Vomiting
may also occur.  Neurologic symptoms are usually first seen between the ages
of 12 and 32 years and are characterized by drooling, difficulty speaking and
poorly articulated words (dysarthria).  Other neurological symptoms may
include difficulty when swallowing (dysphagia), lack of coordination, tremor,
spasticity, muscle rigidity and double vision.

Other symptoms of Wilson's Disease may include kidney stones, joint
disorders and abnormalities of the heart (cardiomyopathy).  It is believed
that a sudden release of copper from the liver may cause an acute crisis in
some patients due to the sudden rapid breakdown of red blood cells
(hemolysis).

The Kayser-Fleischer ring is an important symptom that eventually appears
in the eyes of patients with Wilson's Disease, and especially in patients
with neurologic involvement.  This ring is a rusty-brown deposit in the
corneas of the eyes that may not be present until the later stages of
Wilson's disease.

Neurological signs and symptoms that may appear in the late stages of
Wilson's Disease include decreased cognitive abilities and behavioral
disturbances.   Joint and bone involvement may include a thinning of the
bones (osteoporosis) and the appearance of bony outgrowths (osteophytes) at
large joints.  There may be reduced spinal and extremity joint spaces.
Kidney involvement may include renal tubular damage.

The psychiatric manifestations of Wilson's Disease vary widely from
patient to patient.  These symptoms may be confused with other psychiatric
disorders, ranging from depression to schizophrenia.  Accurate diagnosis is
essential as medications that are commonly given for such disturbances
(phenothiazines) can aggravate the neurologic and psychiatric symptoms of
Wilson's Disease.  The side effects of these drugs may appear similar to
symptoms of Wilson's Disease.  Most patients with the psychiatric symptoms of
Wilson's Disease also have neurologic symptoms and Kayser-Fleischer rings in
the corneas of their eyes.

In adolescent females, menstruation may not begin until the disease is
treated.  This is due to the general disturbances in metabolism caused by
Wilson's Disease.

Causes

Wilson's Disease is inherited as an autosomal recessive genetic trait.  The
defective gene that prevents the liver from adequately excreting copper in
the bile has been located on chromosome 13 at position q14.   Symptoms
develop due to the gradual over-accumulation of copper in the body.

Human traits, including the classic genetic diseases, are the product of
the interaction of two genes, one received from the father and one from the
mother.  In recessive disorders, the condition does not appear unless a
person inherits the same defective gene for the same trait from each parent.
If one receives one normal gene and one gene for the disease, the person will
be a carrier for the disease, but usually will not show symptoms.  The risk
of transmitting the disease to the children of a couple, both of whom are
carriers for a recessive disorder, is twenty-five percent.  Fifty percent of
their children will be carriers, but healthy as described above.  Twenty-five
percent of their children will receive both normal genes, one from each
parent, and will be genetically normal.

Affected Population

Wilson's Disease is a rare disorder that affects males and females in equal
numbers.  The disease is found in all races and ethnic groups.  Wilson's
Disease occurs in approximately 1 in 100,000 people worldwide.  There are
about 2,000 diagnosed cases in the United States.  Many cases are
misdiagnosed, however, usually as mental illness, and the true incidence may
be higher.

Related Disorders

Symptoms of the following disorders can be similar to those of Wilson's
Disease.  Comparisons may be useful for a differential diagnosis:

Sydenham's Chorea is an acute, usually self-limited disorder that occurs
after about 5 to 10 percent of cases of rheumatic fever.  The disorder
typically begins with jerky, uncontrollable, non-repetitive muscle movements
on one or both sides of the body.  Patients develop rapid, involuntary
movements that can affect the manner or style of walking, arm movements and
speech.  Clumsiness and facial grimacing are common.  (For more information on
this disorder choose "Sydenham's Chorea" as your search term in the Rare
Disease Database).

Primary Biliary Cirrhosis is a chronic, progressive disease of the liver
thought to be related to abnormalities in the immune system.  The initial
symptoms of this disorder usually include persistent, generalized itching,
dark urine, pale stools and jaundice.  Eventually, excessive amounts of
copper accumulate in the liver and fibrous or granular hardening occurs in
the soft tissue of the liver.  (For more information on this disorder, choose
"Primary Biliary Cirrhosis " as your search term in the Rare Disease
Database).

Heavy Metal Poisoning is generally caused by industrial exposure to a
variety of toxins such as copper, aluminum, arsenic or mercury.  Depending of
the type and duration of exposure, the injury may occur in the lungs, nervous
system, the skin or digestive system.  The symptoms of the poisoning vary
according to the type of metal that was involved in the overexposure.  These
include headache, nausea, dizziness, painful joints and muscles, delirium,
seizures and a wide range of other symptoms.  (For more information on these
disorders, choose "Heavy Metal Poisoning " as your search term in the Rare
Disease Database).

Levine-Critchley Syndrome is a very rare genetic disorder of the
neuromuscular and blood systems.  Abnormal blood cells (acanthocytosis) are
produced and there is a wasting away (atrophy) of muscles.  The major symptom
of this disorder is uncontrolled rapid muscular movements (amyotrophic
chorea).  Initially there are subtle involuntary movements (tics) of the
face, mouth, and tongue.  These slowly progress to severe, uncontrolled,
rapid motions (chorea) of the trunk and limbs.  Approximately 50 percent of
people with Levine-Critchley Syndrome have seizures.  (For more information
on this disorder, please choose "Levine-Critchley" as your search term in the
Rare Disease Database).

Huntington's Disease (Huntington's Chorea) is an inherited, progressively
degenerative neurological disorder.  Initially there are personality changes
and rapid jerky muscle movements that are involuntary.  In time speech and
memory become impaired and involuntary muscle movements become more frequent
and pronounced.  As Huntington's Disease progresses there is a further loss
of cognitive abilities and dementia.  The symptoms of this disorder usually
begin during adulthood generally after the age of forty.  (For more
information on this disorder choose "Huntington" as your search term in the
Rare Disease Database.)

Tourette Syndrome is a neurologic movement disorder that is characterized
by repetitive motor and vocal tics.  The first symptoms during childhood are
usually rapid eye blinking or facial grimaces.  Symptoms may also include
involuntary movements of the extremities, shoulders, face and voluntary
muscles.  Some people with Tourette Syndrome may vocalize involuntarily;
these may be inarticulate sounds or words.  Tourette Syndrome is not a
progressive or degenerative disorder; symptoms tend to be variable and follow
a chronic waxing and waning course.  Onset is usually begin before the age of
16.  (For more information on this disorder, choose "Tourette" as your search
term in the Rare Disease Database.)

Cerebral Palsy is a neuromuscular disorder that is the result of an
injury to the brain during early development or at birth.  The major symptom
of this disorder is a lack of muscle control and coordination.  Cerebral
Palsy is not a progressive disorder.  Generally infants may exhibit
developmental delays during the first or second year and may have muscle
weakness and abnormal muscle tone.  The coordination and speech difficulties
associated with Wilson's Disease can resemble the symptoms of Cerebral Palsy.
(For more information on this disorder, choose "Cerebral Palsy" as your
search term in the Rare Disease Database.)

Therapies:  Standard

Wilson's Disease is routinely treated with the drug D-Penicillamine.  This
drug causes the excretion of copper into the urine.  Pyrimidine Hydrochloride
(Vitamin B6) is usually prescribed to counteract a side effect of
penicillamine that can make the patient deficient in Vitamin B6.  Treatment
must be continued throughout life to avoid abnormal accumulation of copper.
However, some patients cannot tolerate long-term therapy with penicillamine.

The orphan drug Trien (brand name Cuprid) was approved by the FDA for
treatment of Wilson's Disease in 1985.  The drug is manufactured by Merck,
Sharp and Dohme.  Cuprid is an effective therapy for those Wilson's Disease
patients who cannot tolerate penicillamine.

Physical therapy and speech therapy can be helpful for Wilson's Disease
patients with neurological involvement.  Liver transplants have been
successful in cases of severe liver damage.  A low copper diet is often
advised.  Chocolate, nuts and shell fish are usually high in copper and
should not be eaten in excess.  Diet information can be obtained from the
Wilson's Disease Association.

Genetic counseling will be of benefit for patients and their families.

Therapies:  Investigational

The orphan drug Zinc Acetate is being tested as a maintenance therapy to
treat Wilson's Disease.  Zinc acetate is a common nutritional substance;
however, it must be taken in certain doses at specific times during the day
to affect copper metabolism.  Therefore, careful monitoring by a physician is
necessary to assure effectiveness on Wilson's Disease patients.  Zinc acetate
is manufactured by Lemmon Co., 650 Catarhill Road, Sellersville, PA 18960.
For more information, please contact:

     George J. Brewer, M.D.
     University of Michigan Medical School
     Medical Science #MU708
     Box 0618
     University of Michigan
     Ann Arbor, MI  48109-0618

Investigational studies are underway to determine the effectiveness of
ammonium tetrathiomolybdate as a possible treatment for Wilson's Disease.
This agent is being used for initial rapid "decoppering" of patients with
this disorder.  Further studies are necessary to determine the long-term
safety and effectiveness of this treatment.

This disease entry is based upon medical information available through
November 1992.  Since NORD's resources are limited, it is not possible to
keep every entry in the Rare Disease Database completely current and
accurate.  Please check with the agencies listed in the Resources section for
the most current information about this disorder.

Resources

For more information on Wilson's Disease, please contact:

     National Organization for Rare Disorders (NORD)
     P.O. Box 8923
     New Fairfield, CT 06812-1783
     [phone]

     Wilson's Disease Association
     P.O. Box 75324
     Washington, DC  20013
     [phone]

     American Liver Foundation
     998 Pompton Ave.
     Cedar Grove, N.J. 07009
     [phone]

     The United Liver Foundation
     11646 West Pico Blvd.
     Los Angeles, CA  90064
     [phone]
     [phone]

     Children's Liver Foundation
     14245 Ventura Blvd.
     Sherman Oaks, CA  91423
     [phone]

     NIH/National Institute of Neurological Disorders & Stroke (NINDS)
     9000 Rockville Pike
     Bethesda, MD  20892
     [phone]
     [phone]

For Genetic Information and Genetic Counseling Referrals:

     March of Dimes Birth Defects Foundation
     1275 Mamaroneck Avenue
     White Plains, NY 10605
     [phone]

     Alliance of Genetic Support Groups
     35 Wisconsin Circle, Suite 440
     Chevy Chase, MD  20815
     (800) 336-GENE
     [phone]

References

THE METABOLIC BASIS OF INHERITED DISEASE, 6th Ed., Scriver, Beaudet, Sly, and
Valle; McGraw-Hill; 1989.  Pp. 1416-1421.

MENDELIAN INHERITANCE IN MAN, 10th Ed.:  Victor A. McKusick, Editor:
Johns Hopkins University Press, 1992.  Pp. 1756-1757.

CECIL TEXTBOOK OF MEDICINE, 19th Ed.:  James B. Wyngaarden, and Lloyd H.
Smith, Jr., Editors; W.B. Saunders Co., 1990.  Pp. 1132-1133.

WILSON'S DISEASE, S.E. Woods; Am Family Physician (July 1989; 40(1)):  Pp.
171-178.

WILSON'S DISEASE:  CURRENT STATUS, J.C. Yarse et al.; Am J Med (June 1992;
92(6)): Pp. 643-654.

PATHOPHYSIOLOGY AND TREATMENT OF WILSON'S DISEASE, R.M. Tankanow; Clin
Pharm (Nov 1991; 10(11)):  Pp. 839-849.