What is Wilson disease?

Causes and Symptoms

Wilson disease is an autosomal recessive disorder of copper metabolism, resulting in excess copper accumulation and toxicity in the body. The gene in Wilson disease is located on chromosome 13 and codes for a copper-transporting protein. The normal mechanism of elimination of excess copper in humans is excretion of extra copper in the bile for loss in the stool. The genetic mutation in this disease causes defective, reduced excretion of copper into the bile by the liver. The resultant excessive copper accumulation in the liver and brain causes liver damage and neurologic as well as psychiatric abnormalities.

Wilson disease typically manifests itself between the ages of ten and forty, although it may also appear in earlier childhood as well as later in life. Typical signs and symptoms are related to damage to the liver and brain. Liver involvement in Wilson disease may vary from hepatitis or chronic cirrhosis to acute liver failure. Neurologic symptoms and signs often involve areas of brain that control movement. Patients may have slurred speech, tremor and rigidity in the extremities, and dystonia, a syndrome of sustained muscle contractions causing abnormal postures or movements. Other symptoms include seizures, mental changes, and transient periods of coma. Psychiatric abnormalities may also be prominent and may be the initial presentation. Behavioral changes include impaired school performance, labile moods, depression, and psychosis.

Useful screening tests for Wilson disease include serum ceruloplasmin, twenty-four-hour urine copper, and slitlamp examination for Kayser-Fleischer rings. Blood ceruloplasmin is usually low in Wilson disease, although approximately 10 to 25 percent of patients will have a normal value. Urinary copper values are typically elevated in symptomatic patients. Kayser-Fleisher rings, which are caused by copper deposits in the cornea of the eye, can be detected reliably only by slitlamp microscopy
examination. They are almost always seen in patients with neurologic or psychiatric symptoms but may not be present in patients with symptoms related to liver damage. The gold standard for diagnosis in Wilson disease is liver biopsy, which reveals an elevated amount of copper in the liver.

Treatment and Therapy

Given the diverse initial presentations of Wilson disease, early diagnosis is often difficult. It is important, however, because effective treatments exist. Treatment is aimed toward the prevention of copper accumulation, the reduction of copper absorption through the promotion of its excretion in the urine or bile, or a combination of these mechanisms. Pharmacologic treatments include penicillamine and trientine, two drugs that act by removing copper (chelating agents); zinc, which blocks copper absorption; and tetrathiomolybdate, which is experimental. Liver transplantation can be helpful in the patient with end-stage liver disease.

Bibliography

Brewer, George J. Wilson’s Disease: A Clinician’s Guide to Recognition, Diagnosis, and Management. Boston: Kluwer Academic, 2001.

Hoogenraad, Tjaard U. Wilson’s Disease. Philadelphia: W. B. Saunders, 1996.

"NINDS Wilson Disease Information Page." National Institute of Neurological Disorders and Stroke, June 14, 2012.

Parker, James N., and Philip M. Parker, eds. The 2002 Official Patient’s Sourcebook on Wilson’s Disease. San Diego, Calif.: Icon Health, 2002.

Rosenblum, Laurie, and Michael Woods. "Wilson Disease." Health Library, Apr. 26, 2013.

Rowland, Lewis P., Timothy A. Pedly, and H. Houston Merritt, ed. Merritt’s Neurology. 12th ed. Philadelphia: Lippincott Williams & Wilkins, 2010.

Schilsky, M. L. “Diagnosis and Treatment of Wilson’s Disease.” Pediatric Transplantation 6 (2002): 15–19.

"Wilson Disease." MedlinePlus, May 20, 2013.

"Wilson Disease." National Digestive Diseases Information Clearinghouse (NDDIC), Apr. 30, 2012.