Frequently Asked Questions
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Symptoms
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., Ph.D. Assistant Professor Director, Wilson’s Disease Center of Excellence Clinic at the University of Michigan
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., Ph.D. Assistant Professor Director, Wilson’s Disease Center of Excellence Clinic at the University of Michigan
High serum copper is not an indication of Wilson disease. Since most Wilson patients have a low ceruloplasmin they actually have a lower than normal serum copper. Ceruloplasmin is the protein that binds with copper to remove it from the body. It is the unbound (to ceruloplasmin) copper that is free to roam around the body and accumulate in organs causing Wilson disease damage.
An elevated serum copper is more often due to an elevation of the level of serum ceruloplasmin since it contains ~90% of the circulating copper bound to it. Elevations of ceruloplasmin can occur with inflammation, in response to estrogen therapy and in pregnancy. Note: The exception to this is when there is severe liver injury (acute liver failure) caused by Wilson disease. This causes very large amounts of copper to be released into circulation and causes markedly elevated serum copper. When this occurs, patients are very ill and usually have jaundice (yellow eyes and skin color) and very abnormal lab results with respect to liver function and blood coagulation. – Michael Schilsky, M.D., Weill Cornell School of Medicine, WDA Medical Advisor
Hepatic: Asymptomatic hepatomegaly; Isolated splenomegaly; Persistent elevated AST, ALT; Fatty Liver; Acute hepatitis; resembling autoimmune hepatitis; cirrhosis (compensated or decompensated); fulminant hepatic failure
Neurological: Movement disorders (tremor, involuntary movements); drooling, dysarthria; rigid dystonia; pseudobulbar palsy; seizures; migraine headaches; insomnia
Psychiatric: Depression; neuroses; personality changes; psychosis
Other symptoms: Renal abnormalities: amino-aciduria and nephrolithiasis; skeletal abnormalities: premature osteoporosis and arthritis; cardiomyopathy, dysrhythmias; pancreatitis; hypoparathyroidism; menstrual irregularities: infertility, repeated miscarriages
From: A Diagnostic Tool for Physicians (3/04)
Treatment/Medications
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
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.
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.
It is not uncommon for symptomatic women with Wilson’s disease to suffer irregular periods and multiple miscarriages. These are due to 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.
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. 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 Schilsky, M.D. Weill Cornell School of Medicine WDA Medical Advisor
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 trientine in preference to penicillamine due to the risk of making neurologic disease worse on penicillamine. Physical therapy is also quite important for your treatment plan. – Fred Askari, M.D. Assistant Professor Director, Wilson’s Disease Center of Excellence Clinic at the University of Michigan
The combination of zinc and trientine 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 trientine 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 trientine 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 over treatment: 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 trientine.
Summary: Monitoring patients taking the combination of trientine and zinc is most like monitoring those taking trientine 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
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 trientine 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
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. However, if there has been damage done to the brain cells by copper, this may [or may not] be reversible Michael Schilsky, M.D. Weill Cornell School of Medicine WDA Medical Advisor
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., Ph.D. Assistant Professor Director, Wilson’s Disease Center of Excellence Clinic at the University of Michigan
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., Ph.D. Assistant Professor Director, Wilson’s Disease Center of Excellence Clinic at the University of Michigan
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 lunchmeat generally helps. – Fred Askari, M.D. Assistant Professor Director, Wilson’s Disease Center of Excellence Clinic at the University of Michigan
Complications
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 if Wilson disease is treated and the patient responds to the treatment. – Peter Hedera, M.D. Department of Neurology Vanderbilt University
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 Schilsky, M.D. Weill Cornell School of Medicine WDA Medical Advisor
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 Schilsky, M.D. Weill Cornell School of Medicine WDA Medical Advisor
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., Ph.D., Assistant Professor Director, Wilson’s Disease Center of Excellence Clinic at the University of Michigan
Yes, a heterozygote can donate part of his/her liver if it is otherwise healthy, the blood type is compatible, and there are no other medical contraindications. It must also be known with certainty that the donor is just a carrier and does not actually have Wilson disease. This may need to be determined through genetic testing. There are reported cases of heterozygotes donating in this way in the U.S., China, and Japan. Studies show that this option corrects the abnormality of copper metabolism caused by Wilson disease in the recipients. – Dr. Fred Askari, University of Michigan Dr. Michael Schilsky, Weill-Cornell School of Medicine Dr. Regino Gonzalez-Peralta, University of Florida
Monitoring
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 must be adjusted. – Michael Schilsky, M.D. Weill Cornell School of Medicine WDA Medical Advisor
High urine zinc proves the patient is taking his or her zinc conscientiously. – Michael Schilsky, M.D. Weill Cornell School of Medicine WDA Medical Advisor
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)
Free Copper =8.1(μg/dl)
or
(Total Serum Copper in μmole/L x 63.55) – (Ceruloplasmin in mg/L x 3) = (Free Copper in μg/L ÷ 10) = Free Copper in μg/dl (Normal range is 5 – 15 μg/dl)
Example:
Serum Copper of 6.3(μmole/L) x 63.55 400.3 (μg/L)
Ceruloplasmin of 60 (mg/L) x 3 -180 (μg/L)
Free Copper =220.3 (μg/L)
Free Copper in (μg/L) ÷ 10 =20.3(μg/dl)
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 – Fred Askari, M.D University of Michigan WDA Medical Advisor
Using an acid washed jug goes back to the days when glass containers were used. The purpose of acid washing them was to remove any trace elements that may have been present. Most of the disposable plastic containers used now are not contaminated with trace metals and can be used for collections. In fact, acid washing of jugs can sometimes be a source of contamination if the incorrect wash is used. Preservatives in the jugs are also unnecessary; as trace elements like copper and zinc, do not degrade. Rather, preservatives are used to prevent excessive growth of bacteria that could make testing procedures unpleasant for lab personnel. We recommend using a reputable lab and following their specifications for the 24-hour collection. – Dr. Fred Askari, University of Michigan Dr. Sihoun Hahn, University of Washington WDA Medical Advisors
Twenty four hour creatinine can be measured to double check on the accuracy of the collection. We routinely measure zinc, which also provides a double check. Certainly, if a collection is suspect running a creatine is another check. – Dr. Fred Askari, University of Michigan WDA Medical Advisors
Misc/Other
Over 70 years old. – H. Ascher Sellner, M.D.
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., Ph.D. Assistant Professor Director, Wilson’s Disease Center of Excellence Clinic at the University of Michigan
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., Ph.D. Assistant Professor Director, Wilson’s Disease Center of Excellence Clinic at the University of Michigan
The sequence analysis of ATP7B gene (Wilson disease gene) to identify the mutations is clinically available as a test. Although this is the most updated and thorough test, please be aware that some alterations such as large deletion or duplication may not be detected with this method. It is important that the biochemical testing must be performed prior to genetic tests. – Sihoun Hahn, M.D., Ph.D. University of Washington WDA Medical Advisors
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. 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 https://www.kff.org/health-costs/report/a-consumer-guide-to-handling-disputes-with-your-employer-or-private-health-plan/ 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
It is named after an American neurologist, Alexander Kinnear Wilson, who originally described the disease while working in England in the early part of the 1900’s. – George J. Brewer, M.D. Wilson’s Disease for the Patient and Family
