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Wilson's Disease is a genetic
disorder that is fatal unless detected and treated before
serious illness from copper poisoning develops. Wilson's Disease
affects approximately one in 30,000 people worldwide. The
genetic defect causes excessive copper accumulation in the liver
or brain.
Small amounts of copper are as
essential as vitamins. Copper is present in most foods (see Copper
Content of Various Foods), and most people have much
more copper than they need. Healthy people excrete copper they
don't need but Wilson's Disease patients cannot.
Copper begins to accumulate
immediately after birth. Excess copper attacks the liver or
brain, resulting in hepatitis, psychiatric, or neurologic
symptoms. The symptoms usually appear in late adolescence.
Patients may have jaundice, abdominal swelling, vomiting of
blood, and abdominal pain. They may have tremors and difficulty
walking, talking and swallowing. They may develop all degrees of
mental illness including homicidal or suicidal behavior,
depression, and aggression. Women may have menstrual
irregularities, absent periods, infertility, or multiple
miscarriages. No matter how the disease begins, it is always
fatal if it is not diagnosed and treated.
The first part of the body
that copper affects is the liver. In about half of Wilson's
Disease patients the liver is the only affected organ. The
initial physical changes in the liver are only visible under the
microscope. When hepatitis develops, patients are often thought
to have infectious hepatitis or infectious mononucleosis when
they actually have Wilson's Disease hepatitis. Testing for
Wilson's Disease should be performed in individuals with
unexplained, abnormal liver tests.
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How
is Wilson's Disease Diagnosed?
The diagnosis of Wilson's
Disease is made by relatively simple tests. The tests can
diagnose the disease in both symptomatic patients and people who
show no signs of the disease.
These tests can
include:
- Opthalmalogic slit
lamp examination for Kayser-Fleischer rings
- Serum
ceruloplasmin test
- 24-hour urine
copper test
- Liver biopsy for
histology and histochemistry and copper quantification
- Genetic testing, haplotype analysis for
siblings and mutation analysis.
It is important to
diagnose Wilson's Disease as early as possible, since severe liver
damage can occur before there are any signs of the disease.
Individuals with Wilson's Disease may falsely appear to be in
excellent health. For additional information, refer to the Boston
University Medical Campus website at www.bumc.bu.edu
or consult with your physician.
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How
is
Wilson's Disease Inherited?
Wilson's
Disease is an autosomal recessive disease, which means it is
not sex-linked (it occurs equally in men and women). In order to inherit it, both
of ones parents must carry
a gene that each passes to the affected child. Two abnormal
genes are required to have the disease. At least
one in 30,000 people of all races and nationalities has the
disease.
The responsible gene is
located at a precisely known site on chromosome 13. The gene is
called ATP7B. Some cases of Wilson's Disease occur due to
spontaneous mutations in the gene. Most are transmitted from
generation to generation.
Most patients have no family
history of Wilson's Disease. People with only one abnormal gene
are called carriers. Carriers (heterozygotes) may have mild, but
medically insignificant, abnormalities of copper metabolism.
Carriers do not become ill and should not be treated.
More than 200 different
mutations of ATP7B have been identified thus far. Therefore, it has been
difficult to devise a simple genetic screening test for Wilson's
Disease. However, in a particular family, if the precise
mutation is identified, a genetic diagnosis is possible by
haplotype analysis. This requires a blood sample from both the
patient and a relative. The samples are compared to each other.
Haplotype testing helps to find symptom-free siblings
who have
the disease so that they may be treated before they become ill.
Someday
a genetic test may
help in genetic screening and prenatal diagnosis. However, at this time, there is no
available test for these purposes.
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What is the Likelihood of
Inheriting Wilson's Disease?
One in 100 individuals in the
general population carries one abnormal copy of the Wilson's Disease
gene. Carriers have one normal and one abnormal gene. All
(100%) children of those afflicted with Wilson's Disease receive at least one abnormal copy of the Wilson's Disease gene.
One half (50%) of a carrier's children
receive at least one abnormal copy of the Wilson's Disease gene.
Siblings of
Wilson's Disease patients have a 1
in 4
chance of having the
disease.
Since both of a siblings' parents are carriers,
1/4 of the
siblings' children have the disease, 1/2 are carriers,
and 1/4 are disease free with no Wilson's Disease gene.
Children
of patients have a 1 in 200 chance of having the disease. A
child of a Wilson's Disease patient has a 100% chance of
getting one abnormal gene. The patient's spouse has a 1 in
100 chance of carrying the abnormal Wilson's Disease gene and
half the
time he or she will pass it on.
Grandchildren of
patients have a 1
in 400 chance of
having the disease. A grandchild of a Wilson's Disease patient has a 50% chance
of getting one abnormal gene, since each
a patient's child is a carrier. From the other parent, a
grandchild has a 1 in 200 chance of
getting the
gene (1/2 times 1/200, or 1/400).
Nieces and Nephews of
patients
with siblings who do not have Wilson's Disease have a
1/600 chance of having the disease.
Two-thirds of unaffected siblings carry the gene. The risk
both parents being carriers is 2/3 times 1/100, or 1 in 150. The risk of each of their children having the disease is
1 in 600 (1/4 times 1/150).
Cousins
of Wilson's Disease patients have
a 1 in 800 chance of having the disease.
Fifty
percent of aunts and uncles are carriers.
The risk of both parents of a cousin carrying the abnormal gene is
1/2 times
1/100, or 1 in 200. Since 1 in 4 children of two Wilson's
Disease patients is afflicted, the overall risk of a cousin of a
Wilson's Disease patient being afflicted is 1/4 times 1/200, or
1/800.
All siblings
and
children
of Wilson's Disease
patients should be tested for Wilson's Disease. Other
relatives who have had symptoms or laboratory tests that
indicate liver or neurological disease also should be tested
for Wilson's Disease. People with
Wilson's Disease may not have any signs, symptoms, or evidence
of illness. However,
people with mild or non-apparent
Wilson's Disease will become seriously ill and eventually
die if they are not treated.
Testing is simple and safe. There
are excellent treatments available. Failure to treat Wilson's
Disease causes severe disability and eventually death.
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How
is Wilson's Disease Being Treated?
Wilson's Disease is a very
treatable condition. With proper therapy, disease progress can
be halted and oftentimes symptoms can be improved. Treatment is
aimed at removing excess accumulated copper and preventing its
reaccumulation. Therapy must be lifelong. Patients may become
progressively more sick from day to day, so immediate treatment
can be critical. Treatment delays may cause irreversible damage.
The newest FDA-approved drug
is zinc acetate (Galzin™).
(To link to a page about Galzin, CLICK
HERE.)
Zinc acts
by blocking the absorption of copper in the intestinal tract.
This action both depletes accumulated copper and prevents its
reaccumulation. Zinc's effectiveness has been shown by more than
30 years of considerable experience overseas. A major advantage
of zinc therapy is its lack of side effects.
Other drugs approved for use
in Wilson's Disease include penicillamine (Cuprimine,
Depen) and trientine (Syprine).
(To link to
a page about Cuprimine and Syprine, CLICK
HERE.)
Both of these drugs act by chelation or binding of copper,
causing its increased urinary excretion.
Tetrathiomolybdate is
another chelating drug that is under investigation for initial treatment of Wilson's Disease.
Thus far, it has not caused the neurological worsening
often associated with penicillamine and even with trientine. Patients with severe hepatitis
or liver failure may require liver transplant. Patients being investigated or
treated for Wilson's Disease should be cared for by specialists
in Wilson's Disease or by specialists in consultation with their
primary physicians.
Stopping
treatment completely will result in death, sometimes as quickly
as within three months. Decreasing dosage of medications also
can result in unnecessary disease progression.
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Who Can I Contact
for Help?
There are healthcare
professionals in a variety of countries ready to assist you in
diagnosing and treating Wilson's Disease.
For a listing of physicians
and institutions familiar with Wilson's Disease and/or that accept
Wilson's Disease patients,
CLICK HERE.
For a listing of WDA Centers
of Excellence, CLICK
HERE.
For a listing of individuals who can offer support
to Wilson's Disease patients and families,
CLICK
HERE.
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