Wilson's disease

Definition

Wilson's disease is a rare, inherited disease that causes the body to retain copper. Steadily increasing amounts of copper circulating in the blood are deposited throughout the body in abnormal locations, including in the brain, liver, kidneys, and the cornea of the eyes.

Description

Under normal conditions, copper that finds its way into the body through the diet is processed within the liver. This processed form of copper is then passed into the gallbladder, along with the other components of bile (a fluid produced by the liver, which enters the small intestine in order to help in digestive processes). When the gallbladder empties its contents into the the first part of the small intestine (duodenum), the copper in the bile enters and passes through the intestine with the waste products of digestion. Copper is then passed out of the body in stool.

In Wilson's disease, copper does not pass from the liver into the bile, but rather begins to accumulate within the liver. As copper levels rise in the liver, the damaged organ begins to allow copper to flow into the bloodstream, where it circulates. Copper is then deposited throughout the body, building up, in particular, in the kidneys, the brain and nervous system, and the eyes. Wilson's disease, then, is a disorder of copper toxicity.

Causes & symptoms

Wilson's disease is an inherited disorder, passed in families as a recessive trait (meaning that an individual must receive a defective gene from both his or her mother and father in order to actually have symptoms of the disease). The gene defect is believed to result in an abnormal protein within liver cells that binds to copper, retaining it in the liver. Patients with Wilson's disease also frequently have decreased amounts of a protein, called ceruloplasmin, that carries copper through the bloodstream.

Signs of copper toxicity begin to display themselves between the ages of 5 and 20, with adolescence being the most common time period for diagnosis. Occasionally, individuals have been as old as 50 years before their symptoms have led to diagnosis.

About half of all patients experience their first symptoms in the liver. The illness causes swelling and tenderness of the liver, sometimes with fever, mimicking more common disorders, such as viral hepatitis and infectious mononucleosis. Abnormal levels of circulating liver enzymes reveal that the liver is being seriously damaged. This form of damage is referred to as "fatty degeneration." Without medical intervention, the liver damage will progress to actual cirrhosis. An often fatal manifestation of liver disease is called "fulminant hepatitis." This extremely severe inflammation of the liver (hepatitis) results in jaundice, fluid leaking into the abdomen, low protein circulating in the blood, abnormalities of the blood clotting system, swelling of the brain, and anemia due to the abnormal destruction of red blood cells.

Half of all patients experience their first symptoms due to deposits of copper in the brain and nervous system. These symptoms include tremors, uncontrollable movements of the limbs, stiffness, drooling, difficulty swallowing, difficulty talking, and headache. Many patients have a variety of psychiatric symptoms, suddenly displaying bizarre and inappropriate behavior, with deterioration of functioning at work or school.

A very small percentage of women have symptoms involving their reproductive systems. Some females never begin to have menstrual periods, while others stop having them. Still other women experience multiple miscarriages of pregnancies.

Diagnosis

Because Wilson's disease is so rare, diagnosis is often unfortunately delayed. Physical examination will reveal a unique, characteristic ring of copper deposited in a membrane of the cornea (referred to as Kayser-Fleischer rings). Laboratory examination of the blood will reveal low levels of ceruloplasmin, a glycoprotein in the blood. Liver biopsy will reveal a high concentration of copper. Most medical criteria state that any combination of two of these signs (presence of Kayser-Fleischer rings, low ceruloplasmin, high concentration of copper in liver) is sufficient for a diagnosis of Wilson's disease. Other tests are also useful, for example measuring the quantity of copper passed into the urine daily (high in Wilson's disease). Another lab test measures the ability of a sample of a patient's ceruloplasmin to bind with a form of copper (decreased in Wilson's disease).

Treatment

Treatment involves life-long administration of either D-penicillamine (most commonly) or trientine hydrochloride. Both of these drugs remove copper deposits throughout the body, and bind to the copper to decrease its toxic effects.

Penicillamine has a number of serious side effects:

• Joint pain
• Neurological problems
• Systemic lupus erythematosus
• Decreased production of all blood elements
• Interference with clotting
• Allergic reactions.

Careful monitoring is necessary. When patients have side effects from penicillamine, the dose can sometimes be lowered to an effective level that causes fewer difficulties. Alternatively, steroid medications may be required to reduce certain sensitivity reactions. Trientine has fewer potential side effects, but must still be carefully monitored.

Prognosis

Without treatment, Wilson's disease is always fatal. With treatment, symptoms may continue to worsen for the first six to eight weeks. After this time, definite improvement should begin to be seen. However, it may take several years (two to five) of treatment to reach maximal benefit to the brain and liver. Even then, many patients are not returned to their original level of functioning. Interruptions in treatment can result in a relapse of the disease which is not reversible, and can ultimately lead to death.

Key Terms

Bile

A substance produced by the liver, and concentrated and stored in the gallbladder. Bile contains a number of different substances, including bile salts, cholesterol, and bilirubin. After a meal, the gallbladder pumps a quantity of bile into the duodenum, to keep the intestinal contents at a pH optimal for digestion, and to help breakdown fats.

Ceruloplasmin

A protein circulating in the bloodstream that binds with copper and transports it.

Cirrhosis

A liver disorder most common among alcoholics, in which the structure of the liver is permanently destroyed and distorted by swelling and fibrous scar tissue formation.

Gallbladder

A small, pear-shaped organ in the upper right hand corner of the abdomen. It is connected by a series of ducts (tube-like channels) to the liver, pancreas, and duodenum (first part of the small intestine). The gallbladder receives bile from the liver, and concentrates and stores it. After a meal, bile is squeezed out of the gallbladder into the intestine, where it aids in digestion of food.

Hepatitis

An inflammation of the liver that can be caused by viruses or exposure to toxic agents.

Further Reading

For Your Information

Books

• Scheinberg, I. Herbert. "Wilson's Disease." In Harrison's Principles of Internal Medicine, 14th ed., edited by Anthony S. Fauci, et al. New York: McGraw-Hill, 1998.

  Periodicals

• Hariharan, Ramesh, and L. Fred Herbert. "Wilson's Disease." Hospital Practice 31(August 15, 1996): 556+.

  Organizations

• American Liver Foundation. 1425 Pompton Avenue, Cedar Grove, NJ 07009. (800) 465-4837 or (888) 443-7222.
• Wilson's Disease Association. 4 Navaho Drive, Brookfield, CT 06804. (800) 399-0266.

Gale Encyclopedia of Medicine. Gale Research, 1999.