Wilson’s Disease

By Stephen Holt, MD, PhD, FACP

• What is Wilson’s Disease?
• Causes
• Who is at Risk?
• How Do I Know if I Have It?
• How is it Diagnosed?
• Treatment
• Side Effects From Medications
• Long Term Prognosis?
• Suggested Articles

What is Wilson’s Disease?

Also known as hepatolenticular degeneration, Wilson’s Disease is a rare, inherited disease that causes accumulation of large amounts of copper to be stored in the body, mainly the liver and the brain.

Causes

In order to maintain good health, our body collects copper from foods we eat. Normally, the liver excretes extra copper the body doesn’t need into bile, a digestive juice made by the liver, but for people who have Wilson’s Disease, there is a decreased secretion of copper into the bile causing it to build up in the liver. After enough damage to the liver, the copper is released directly into the bloodstream which carries the copper throughout the body. If not treated, it can cause brain damage, liver failure and death.

Who is at Risk?

Wilson’s Disease is an equal opportunity condition – meaning it doesn’t target a particular race or ethnicity and it affects both males and females. With about one in 40,000 people affected, only those individuals inheriting two mutant forms of the Wilson Disease gene, known as ATP7B, will have the disease. To develop the disease, you must inherit one defective gene from each parent. If you receive only one abnormal gene, you won’t become ill yourself, but you’re considered a carrier and can pass the gene to your children.

How Do I Know if I Have It?

Present at birth, symptoms usually appear between the ages of 6 and 20 but can begin as late as forty. Very rarely, patients with Wilson’s Disease may not have symptoms until they are in their fifties. The most characteristic sign is a rusty brown ring around the cornea of the eye called the Kayser-Fleischer ring. This can be seen only through an eye exam.

Depending on what parts of the body are affected, other symptoms include:

• Fatigue
• Depression
• Joint Pain
• Loss of appetite
• Clumsiness
• Difficulty speaking
• Difficulty swallowing
• Difficulty walking
• Skin rash
• Swelling of the arms and legs
• Bruising
• Yellowing of the skin and eyes (jaundice)
• Drooling
• Involuntary shaking or tremors
• Nausea and/or vomiting

How is it Diagnosed?

Aside from physical symptoms which may indicate the presence of  Wilson’s Disease, medical tests will reveal other symptoms such as swelling of the liver and spleen; fluid buildup in the lining of the abdomen; anemia and low platelet and white blood cell count in the blood.

It is suggested that Wilson’s Disease should be suspected in all young individuals who present with liver disease – especially if there is a family history of liver disease. Because it also causes neurological and psychiatric disorders, any family history of those conditions should raise suspicion of Wilson’s Disease as well. A physical examination and laboratory tests are performed to establish the diagnosis.

• Eye examination. Using a special light called a slit lamp, the physician will look for Kayser-Fleischer rings in the eyes which are almost always present in all patients with Wilson’s Disease and neurological symptoms but may not be present in patients suffering from liver disease only.
• Laboratory tests. Blood, urine and liver tissue specimens will be collected. Blood tests will be performed to look for copper in the blood and to monitor liver function and a 24-hour urine collection will be tested to measure the amount of copper being excreted in the urine. A liver biopsy (small sample of liver tissue removed from the liver using a long thin needle) may be performed to test for excess copper.
• Genetic testing. For those individuals with a family history of Wilson’s Disease, genetic testing may be helpful in making a diagnosis. A DNA mutation analysis blood test can identify the genetic mutations that cause Wilson’s Disease thereby allowing asymptomatic family members to be tested and treated early before disabling symptoms begin.  

Because it causes a wide variety of symptoms which could be mistaken for other diseases and conditions, it is advisable to see a doctor immediately if any of the listed symptoms are present and it is especially important to inform the doctor if any family member has Wilson’s Disease.

Treatment

Once a diagnosis is confirmed, lifelong treatment will be necessary in order to prevent copper from accumulating in the liver again.

Treatment includes the following:

• Low Copper Diet. Avoiding foods rich in copper will most likely be recommended such as shellfish, nuts, chocolate, mushrooms, dried fruit, liver, dried peas, beans, lentils, avocados, and bran products. Also, eliminating the use of copper pots and pans and storage containers is suggested.
• D-penicillamine. A chelating agent sold under the trade names Cuprimine and Depen, D-penicillamine removes excess copper from the body by binding to the copper and increasing urinary output to rid the body of excess amounts of copper.
• Trientine. Also a chelating agent sold under the trade name Syprine, Trientine works much the same as D-pencillamine by binding to the copper and increasing urinary output to rid the body of excess amounts of copper.
• Zinc acetate. Zinc acetate blocks the absorption of copper and increases copper excretion in the stool. Often used for people who have been successfully treated with chelation agents, zinc acetate is often used to maintain healthy levels of copper in the body and for asymptomatic individuals to prevent progression of the disease.
• Ammonium Tetrathiomolybdate. An agent previously used to treat copper toxicosis (poisoning) in animals, ammonium tetrathiomolybdate is also effective in treating Wilson’s Disease. However, it is still considered an experimental drug, and is not readily available.
• Liver Transplant. For individuals with cirrhosis, end-stage liver disease and sudden-onset liver failure caused by Wilson’s Disease, a liver transplant may be necessary.

Symptomatic treatment for symptoms of muscle spasm, stiffness, and tremor may include anticholinergics, tizanidine, baclofen, levodopa, or clonazepam (parasympathetic nerve blockers, muscle relaxants, anti-spasmodics, and anti-convulsants).

For individuals who have been diagnosed but are asymptomatic, chelating agents may be administered to reduce the amount of liver damage. Once symptoms are under control, a lower dosage of drugs may be prescribed to control the amount of copper retained by the body.

Side Effects From Medications

D-penicillamine can cause serious side effects such as fever, skin rash, lymphadenopathy (disease of the lymph nodes), bone marrow suppression, worsening of neurological symptoms and birth defects. Trientine is considered to be a safer alternative to D-penicillamine because it has fewer or milder side effects. While advocated for its lower toxic profile, long term safety and efficacy of ammonium tetrathiomolybdate is unknown.

Long Term Prognosis?

Wilson’s Disease requires lifelong treatment. However, if diagnosed early or while asymptomatic, individuals who start and continue drug treatment can prevent all complications of the disease including the reversal of neurological and psychiatric symptoms and some aspects of liver damage. For those individuals with Wilson’s Disease who have cirrhosis and end-stage liver disease, liver transplantation may be necessary.

This information is for educational purposes only and should not be used in any other manner. This information is not intended to substitute for informed medical advice. You should not use this information to diagnose or treat a health problem or disease without consulting with a qualified health care provider.

Suggested Articles

• What You Need to Know About Jaundice
• Exposing 5 Common Myths About Liver Disease

About the Author

Stephen Holt, MD, PhD, FACP

Stephen Holt, M.D. is a Distinguished Professor of Medicine NYCPM (Emerite) and a medical practitioner in New York State. He has published many peer-review papers in medicine and he is a best-selling author with more than twenty books in national and international distribution. He has received many awards for teaching and research. Dr. Holt is a frequent lecturer at scientific meetings and healthcare facilities throughout the world. He is a best selling author and the founder of the Holt Institute of Medicine.