Wilson Disease

What is Wilson disease?

Wilson disease (WD) is a rare inherited disorder of copper metabolism in which excessive amounts of copper accumulate in the body.

The buildup of copper leads to damage in the liver, brain, and eyes. Although copper accumulation begins at birth, symptoms of the disorder only appear later in life.

The most characteristic sign of WD is the Kayser-Fleisher ring—a rusty brown ring around the cornea of the eye that can best be viewed using an ophthalmologist’s slit lamp.

The primary consequence for most individuals with WD is liver disease, appearing in late childhood or early adolescence as acute hepatitis, liver failure, or progressive chronic liver disease in the form of chronic active hepatitis or cirrhosis of the liver.

In others, the first symptoms are neurological, occur later in adulthood, and commonly include slurred speech (dysarthria), difficulty swallowing (dysphagia), and drooling.

Other symptoms may include tremor of the head, arms, or legs; impaired muscle tone, and sustained muscle contractions that produce abnormal postures, twisting, and repetitive movements (dystonia); and slowness of movements (bradykinesia). Individuals may also experience clumsiness (ataxia) and loss of fine motor skills.

One-third of individuals with WD will also experience psychiatric symptoms such as an abrupt personality change, bizarre and inappropriate behavior, depression accompanied by suicidal thoughts, neurosis, or psychosis.

WD is diagnosed with tests that measure the amount of copper in the blood, urine, and liver.

Is there any treatment?

WD requires lifelong treatment, generally using drugs that remove excess copper from the body and prevent it from re-accumulating. Zinc, which blocks the absorption of copper in the stomach and causes no serious side effects, is often considered the treatment of choice.

Penicillamine and trientine are copper chelators that increase urinary excretion of copper; however, both drugs have some side effects.

Tetrathiomolybdate is an investigational copper chelating drug with a lower toxicity profile, but it has not been approved by the Food and Drug Administration for the treatment of WD and its long-term safety and effectiveness aren’t known.

A low-copper diet is also recommended, which involves avoiding mushrooms, nuts, chocolate, dried fruit, liver, and shellfish.

In rare cases where there is severe liver disease, a liver transplant may be needed. Symptomatic treatment for symptoms of muscle spasm, stiffness, and tremor may include anticholinergics, tizanidine, baclofen, levodopa, or clonazepam.

What is the prognosis?

Early onset of the disease may foretell a worse prognosis than later onset. If the disorder is detected early and treated appropriately, an individual with WD can usually enjoy normal health and a normal lifespan. If not treated, however, WD can cause brain damage, liver failure, and death. The disease requires lifelong treatment.

What research is being done?

The National Institute of Neurological Disorders and Stroke, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and other institutes of the National Institutes of Health (NIH) conduct and/or support research related to Wilson disease. Growing knowledge of the copper transporting gene ATP7B, which in its mutated form causes WD, should lead to the design of better therapies for this disorder.