Index to
Frequently Asked Questions
Brain
damage
Chelation
Copper
IUDs
Copper
levels in drinking water
Cognitive
decline
Dementia
Dietary
supplements
Disputes
over health insurance
Drinking
water, copper levels in
Dystonia
Galzin
shelf life
Health
insurance disputes
Hepatitis
vaccine
IUDs,
copper
Liver
damage
Liver
transplants
Miscarriage
Memory
loss
Movement
disorder
Overview
Penicillamine
healing after surgery
Pregnancy
miscarriages
Proteinuria
Serum Free Copper
Supplements,
dietary
Tizanidine
Treatment,
general
Galzin
Penicillamine
zinc
Trientine
Trientine
Ulcers
Zinc
accumulation in the body
and nausa
and ulcers
high levels in urine
in combination with trientene
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General Questions
about Wilson's Disease
Can you provide an overview
of how Wilson's Disease affects the liver?
The course of liver disease in Wilson's disease stands in contrast to other
forms of cirrhosis for many people. The chronic liver injury in Wilson's
disease is caused by excess free copper, and the liver disease often
stabilizes or even improves once the excess copper is treated with zinc
acetate maintenance therapy. While some people do progress to need liver
transplantation, others may actually see long term improvement in their
liver function over time. It is important to be attentive to issues such as
immunizations for viral hepatitis, avoiding excess alcohol consumption, and
treating complications of portal hypertension in order to give the liver its
best chance to mend.
Fred Askari, M.D.
Assistant Professor
Director, Wilson's Disease Center of Excellence
Clinic at the University of Michigan
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How old
is the oldest newly diagnosed Wilson's Disease patient?
Over 70
years old.
H. Ascher
Sellner, M.D.
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Can
Wilson's Disease result in permanent brain damage leading to memory
loss?
I am a neurologist and I have seen many
Wilson's Disease patients. Even though Wilson's Disease is primarily classified and considered as a
"movement disorder," cognitive decline is very common. The analogy is with
Parkinson disease, where some patients develop "subcortical
dementia." The subject of dementia/cognitive decline in
Wilson's Disease has not been studied that well but some papers about this have been published. Basically, what is going on
is the disruption of projections of the basal ganglia to the prefrontal
cortex. This may be reversible is Wilson's Disease is treated and the patient responds to
the treatment.
Peter Hedera,
M.D.
University of Michigan
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Is there one side
of the brain or location in the brain that is more or less
adversely affected as a result of the copper accumulation?
Generally, the brain
is affected symmetrically with excess copper deposition,
although symptoms can be worse on one side of the body than
another. This may have to do with factors of asymmetric
neurologic development, such as being right or left handed.
The copper is often
seen most prominently in the basal ganglia, the area deep within
the brain that coordinates movements. The face of the giant
panda sign refers to a characteristic appearance of the basal
ganglia in advanced Wilson's Disease. This is a description of
the appearance of the basal ganglia wherein one can get an
impressionists image of the face of a giant panda.
Fred Askari,
M.D.
Assistant Professor
Director, Wilson's Disease Center of Excellence
Clinic at the University of Michigan
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What
copper levels in drinking water are potentially hazardous for
Wilson's Disease patients?
If
the water is over 0.1 ppm (parts per million) (which is 0.1
mg/L),
I recommend an alternative source.
While 0.1 ppm isn't particularly hazardous, it indicates
that significant copper is coming from somewhere, and at certain
times or under certain circumstances the
level might be quite a bit higher.
George J.
Brewer, M.D.
Department of Human Genetics,
University of Michigan Medical School
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To whom
do I turn for help resolving disputes over health insurance?
With the
vast majority of Americans getting their health care through
some form of managed care plan, understanding those plans and
how to resolve disputes is critical. Today, 40 states plus the
District of Columbia have legislated procedures for resolving
disputes outside the health plan through "external
review" systems, yet studies show these systems are not
well utilized. This guide will help consumers navigate their
plan's internal grievance procedure, as well as their state's
external review process.
"Disputes
with health plans range from simple communication problems to
delays or denial of coverage or care, and it is critical that
consumers have the tools they need to navigate the dispute
resolution process," said Drew Altman, Ph.D., president of
the Kaiser Family Foundation. "Health disputes left
unresolved can have a major impact on people's lives."
A recent
survey by the Kaiser Family Foundation and Harvard University
School of Public Health found that almost half (48%) of
privately insured adults under age 65 had a problem with their
health plan in the last year with a range of consequences from
hassles, to paying more, to adverse effects on their health.
"Consumers
must be vigilant in monitoring the decisions made by health
plans," said Trudy Lieberman, director of The Center for
Consumer Health Choices at Consumers Union. "Many disputes
arise because people don't know their coverage. By becoming
familiar with coverage, benefits and grievance procedures, a
dispute that occurs can be resolved more easily."
A free
online consumer guide about handling health plan disputes has
been launched by the Kaiser Family Foundation and Consumers
Union, the publisher of Consumer Reports magazine. A Consumer
Guide to Handling Disputes With Your Private or Employer Health
Plan provides practical information to plan enrollees who are
seeking a way to resolve a dispute with their health plan or to
better understand their coverage before a problem arises.
The guide
includes sections that will help people understand their health
plan's rules and coverage, its internal review process, and the
external review process in the states that have one. It was
developed under a partnership between The Center for Consumer
Health Choices at Consumers Union and the Kaiser Family
Foundation.
To access
the Consumer Guide, visit the Kaiser Family Foundation website
at http://www.kff.org/consumerguide/
or the health section of the Consumers Union website at http://www.consumersunion.org.
In addition, a link to the Consumer Guide is posted in the free
consumer advice section of the Consumer Reports magazine
website, http://www.consumerreports.org.
For further
information, please contact Jennifer Webber, Kaiser Family
Foundation at 650-854-9400 or Joan Tripi, Consumers Union at
914-378-2436.
The Kaiser
Family Foundation is an independent, national health
philanthropy dedicated to providing information and analysis on
health issues to policymakers, the media, and the general
public. The Foundation is not associated with Kaiser Permanente
or Kaiser Industries.
Consumers
Union is an independent, nonprofit testing and
information-gathering organization, serving only the consumer.
Diane E.
Dorman
Senior Director for Public Policy
National Organization For Rare Disorders - Washington Office
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Should
Wilson's patients receive Hepatitis A or Hepatitis B vaccine?
Yes. Since
Wilson's Disease often affects the liver, many Wilson’s
Disease patients cannot afford additional injury to the liver.
Hepatitis A or Hepatitis B vaccine is as safe for Wilson's
Disease patients as it is for others.
H. Ascher
Sellner, M.D.
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It is not uncommon for symptomatic women with Wilson's disease to suffer irregular periods and multiple miscarriages. These are the consequences of malfunction of the liver causing hormonal changes which are reversible with successful treatment of the underlying disorder. But is the treatment hazardous for the fetus?
Review of the literature and personal experience indicate that women successfully treated with either penicillamine, trientine or zinc uninterruptedly, have excellent chances for carrying through uncomplicated pregnancies and for delivering normal babies. However, precautions are indicated in women with dilated veins in the stomach or esophagus which may rupture and bleed because of the increased abdominal pressure caused by the enlarging uterus.
There is no report of an untoward reaction to a baby nursed while the mother continued on an anti-copper regimen.
H. Ascher
Sellner, M.D.
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Are
copper IUDs safe for Wilson's Disease patients?
The IUD is
plastic with copper wound around it. I would not advise it in
women Wilson's Disease patients. There are progesterone
containing IUDs, one of which was just released, that are good
for five years instead of one to two years.
H. Ascher
Sellner, M.D.
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Treatment
Questions
With what medication should
the Wilson’s Disease patient begin treatment?
There are
now new options for the medical treatment of patients with
Wilson's Disease. Penicillamine is no longer the "treatment
of choice," as there is a growing experience with safer and
effective alternatives. Trientine may be the best first choice
amongst currently approved drugs as initial therapy for
symptomatic patients requiring chelation therapy, and may be
even more effective when used in combination with zinc
treatment. Tetrathiomolybdate is undergoing clinical testing for
use in the initial treatment of patients with neurologic
symptoms. Zinc is an effective medication for maintenance
therapy. Further studies are needed to determine the best
therapy for pregnant patients with Wilson's Disease, and whether
combination therapy using trientine and zinc will be the next
"treatment of choice" for all symptomatic patients
with liver or neurologic disease.
Michael L.
Schilsky, M.D.
Division of Liver Diseases and Recanati/Miller Transplant
Institute
The Mount Sinai School of Medicine
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Will
Tizanidine help control or reduce dystonia?
Medications
we commonly use to control the symptoms of dystonia are Klonipin
and Artane. Tizanidine may be reasonable to try as well.
Obviously, an examining physician must decide what is best to
try for each patient's individual condition. We also use zinc
acetate or at times trientene in preference to penicillamine due
to the risk of making neurologic disease worse on penicillamine.
Consider
getting Dr. Brewer's book on the treatment of Wilson's disease.
It has a lot of advice for doctors treating Wilson's disease and
may help you and your physician decide on the best course of
action. For information on where to obtain the book, I suggest
you email Dr Brewer directly at gbrewer@umich.edu.
Physical therapy is also quite important for your son's
treatment plan.
Fred Askari,
M.D.
Assistant Professor
Director, Wilson's Disease Center of Excellence
Clinic at the University of Michigan
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Can
Zinc and Trientene be used in combination?
The
combination of zinc and trientene can be used for the first four
months of therapy in patients with significant liver or
neurologic disease. How often you check lab values depends on
the extent of disease, the range can be from weekly checks of
urine copper and zinc to every three months after initiating
treatment. Subsequently, the urine copper and zinc could be
checked every six months for two years, then annually with more
frequent checks if compliance is in doubt.
Urine copper levels
should be in the range expected for treatment with trientene
alone, in other words 1-2 mg /24 hours initially and then
reducing to 0.5-1.0 mg after several months of treatment. We
look at the trend in urine values over time as much as the
absolute numbers at any one time to gauge compliance and
treatment effectiveness at reducing copper.
You
also can monitor the non-ceruloplasmin copper. This frequently
falls to less than 10 micrograms/dl on the combination therapy.
Monitoring
for compliance: The urine zinc should be over 2.0 mg with
adequate compliance with zinc treatment. Compliance with
trientene is gauged by an initial increase in urine copper when
the medicine is first started followed by a drop in urine copper
values over time.
Monitoring
for overtreatment: Be concerned if the urine copper is less than
35, consider in the presence of anemia or decreased white blood
count. On combination therapy, the urine copper may be higher
than 35 in the presence of copper deficiency, so watch for
unexplained anemia or decreased white blood count.
Monitoring
for toxicity: Watch for gastric side effects from zinc such as
nausea. Watch for proteinuria, bone marrow suppression and
autoimmune disease with trientene.
Summary:
Monitoring patients taking the combination of trientene and zinc is most like monitoring those
taking trientene alone. The main difference is an increase in urine zinc
should be seen to demonstrate compliance with zinc treatment.
Fred Askari,
M.D.
Assistant Professor
Director, Wilson's Disease Center of Excellence
Clinic at the University of Michigan
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How
long should Zinc
and Trientene be used in combination?
In our experience, the combination of zinc and trientine is not necessary
beyond the initial four to six month period of removing free copper stores.
Zinc maintenance therapy works well for most people thereafter.
Obviously, treatment programs and decisions need to be individualized.
Nevertheless, I am not aware of compelling data to suggest that there is any
need for taking the combination of zinc and trientene long term for the
majority of people.
Fred Askari,
M.D.
Assistant Professor
Director, Wilson's Disease Center of Excellence
Clinic at the University of Michigan
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Will
Galzin dissolve and remove the already accumulated copper in the
brain or is it only effective controlling the further accumulation of copper?
With zinc treatment there is a negative copper balance.
More copper goes out than in, so in time all extra stores of copper, even in the
brain, are removed. Proof of this is the loss of Kayser-Fleischer rings in treated patients with time on zinc.
Michael L.
Schilsky, M.D.
Division of Liver Diseases and Recanati/Miller Transplant
Institute
The Mount Sinai School of Medicine
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Are there any problems with
zinc collecting in the body over time?
Dr. Brewer has over two decades of experience using zinc to treat Wilson's
disease, and the zinc levels in the body increase slightly initially but
zinc does not accumulate over time. We know this from repeat measurements
including repeat liver biopsies which were used to measure liver copper
and zinc to answer this very question. In short, the main concern with
long term treatment with zinc (as well as a concern with all other forms
of treatment of Wilson's Disease) would be the potential for over
treatment which may lead to copper deficiency. Fortunately, this is
relatively unusual but we monitor 24-hour urine copper and zinc levels to
avert this from happening on at least an annual basis. If copper levels
get too low, zinc doses can be reduced before the symptoms of copper
deficiency, primarily manifested as anemia, ensue.
The best
approach is keep taking your zinc and check your urine copper and zinc at least
once a year.
Fred Askari,
M.D.
Assistant Professor
Director, Wilson's Disease Center of Excellence
Clinic at the University of Michigan
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What
percentage of Wilson's Disease patients need
liver transplants?
Only about 5% of patients with Wilson's disease need transplants.
Two thirds are those presenting with liver failure. The remainder are those discovered with
severe liver disease that doesn't respond well to medical therapy, those who stop therapy and deteriorate, or those that experience severe complications of cirrhosis such as frequent GI bleeding from varices due to portal
hypertension or low oxygenation due to hepatopulmonary syndrome.
Michael L.
Schilsky, M.D.
Division of Liver Diseases and Recanati/Miller Transplant
Institute
The Mount Sinai School of Medicine
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Since the
body requires a certain level of copper to function properly,
what is the result if too much copper is removed through
chelation?
When too much copper is removed, then there can be reductions in blood
counts and inhibition of wound healing, amongst other possible effects. This is
the reason that blood counts should be periodically monitored. The amount of
copper can be gauged by reviewing the patterns of the 24- hour urine copper
excretion as well as looking for the "non-ceruloplasmin" copper in the blood-- this
being done by a simultaneous measure of ceruloplasmin and serum copper. When
these values are too low, excluding the possibility of non-compliance which can
alter the interpretation of the urine copper excretion, then the dosages of
treatments must be readjusted.
Michael L.
Schilsky, M.D.
Division of Liver Diseases and Recanati/Miller Transplant
Institute
The Mount Sinai School of Medicine
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What does
high urine zinc mean?
High urine
zinc proves the patient is taking his or her zinc conscientiously.
Michael L.
Schilsky, M.D.
Division of Liver Diseases and Recanati/Miller Transplant
Institute
The Mount Sinai School of Medicine
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What
level of liver recovery can I expect with treatment?
The course
of liver disease in Wilson's Disease stands in contrast to other
forms of cirrhosis for many people. The chronic liver injury in
Wilson's disease is caused by excess free copper, and the liver
disease often stabilizes or even improves once the excess copper
is treated with zinc acetate maintenance therapy. While some
people do progress to need liver transplantation, others may
actually see long term improvement in their liver function over
time. It is important to be attentive to issues such as
immunizations for viral hepatitis, avoiding excess alcohol
consumption, and treating complications of portal hypertension
in order to give the liver its best chance to mend.
Fred Askari,
M.D.
Assistant Professor
Director, Wilson's Disease Center of Excellence
Clinic at the University of Michigan
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How long
does Galzin last?
Galzin
capsules should last indefinitely, so long as they do not
physically fall apart. Zinc itself is an element, so it does not
deteriorate over time.
Fred Askari,
M.D.
Assistant Professor
Director, Wilson's Disease Center of Excellence
Clinic at the University of Michigan
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Is is safe to use outdated
drugs to treat Wilson's Disease?
There are virtually no reports
of toxicity from degradation products of outdated drugs. How
much of their potency they retain varies with the drug and the
storage conditions, especially humidity, but many drugs stored
under reasonable conditions retain 90% of their potency for at
least five years after the expiration date on the label, and
sometimes much longer.
H. Ascher
Sellner, M.D.
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Should
Wilson's Disease patients use weight-gaining supplements to help
maintain their weight?
Metabolic enhancers like pro-kinetic are dangerous for people with liver
disease, they can cause liver failure even in healthy people. Many dietary supplements like Ensure, etc.,
also contain copper supplements. If you are trying to gain weight and have been on
appropriate therapy, drinking one can of Vanilla Boost Plus per day should
not give you too much copper. You also can make your own high calorie
drinks by mixing protein supplements with a milk shake.
Fred Askari,
M.D.
Assistant Professor
Director, Wilson's Disease Center of Excellence
Clinic at the University of Michigan
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Do patients
taking penicillamine have a difficult time in general healing from surgery?
For all surgical procedures, it is recommended that the dosage of
penicillamine be temporarily reduced to 250-500 mg per day until wound healing is
achieved. Similarly, the dosage should be reduced during the last trimester
pregnancy and until wound healing after childbirth is achieved.
No such dosage reduction is needed for zinc treatment.
Michael L.
Schilsky, M.D.
Division of Liver Diseases and Recanati/Miller Transplant
Institute
The Mount Sinai School of Medicine
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How can
Wilson's Disease patients reduce possible nausa and indigestion
when taking zinc?
I suggest that you take a small
piece of lunch meat (turkey, bologna, ham, etc.) with your first morning
dose of zinc. This should help settle your stomach. Do not take any
carbohydrate (bread, etc.) with the dose--this is very important!
The nausea usually abates as treatment persists. Occasionally, someone
finds that nausea to persist, but lunch meat generally helps.
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Does zinc
cause ulcers?
Zinc does not cause ulcers, but ulcers are common problems.
Patients experiencing abdominal pain and nausea should consult with
their gastroenterologist.
Fred Askari,
M.D.
Assistant Professor
Director, Wilson's Disease Center of Excellence
Clinic at the University of Michigan
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How
to calculate serum free copper
The
amount of serum free copper is the amount of copper
circulating in the blood which is unbound by ceruloplasmin.
This is the copper which is "free" to accumulate in
the liver and other organs. Most reference labs do not
automatically calculate the amount of serum free copper
in a Wilson's disease patient's lab report.
To
calculate serum free copper, use the following formula:
(Total Serum Copper in µg/dl) - (Ceruloplasmin in mg/dl
x 3) = Free Copper (Normal range is 5 - 15 µg/dl)
Example:
Serum
Copper of 22.2 (µg/dl) |
22.2 (µg/dl)
|
Ceruloplasmin
of 4.7 (mg/dl) x 3 |
-14.1
(µg/dl)
|
=
8.1 (µg/dl) Free Copper
NOTE:
There are often lab variations in the determination
of ceruloplasmin and sometimes negative values are found.
Some labs will not report the low serum coppers. If
a patient has a very low ceruloplasmin, this formula
may not be useable to determine free copper.
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