RxPG - Wilson's disease

Wilson's disease is an autosomal recessive hereditary disease, with an incidence of about 1 in 30,000. The estimated heterozygous carrier rate is about 1 in 90, meaning that 1 in 90 people are unaffected carriers of this defective gene. The disease affects men and women equally and occurs in all races.

Description

The Wilson's disease gene (WND) has been mapped to chromosome 13 (13q14.3) (2) and is expressed primarily in the liver, kidney, and placenta but has also been found in the heart, brain, and lung, albeit at much lower levels. The gene codes for a P-type adenosinetriphosphatase that transports copper into bile and incorporates it into ceruloplasmin.

The mutant form of WND expressed in people with Wilson's disease inhibits the release of copper into bile. Bile is a liquid produced by the liver that helps with digestion. As the excretion of copper from the body is thus impaired, the copper builds up in the liver and injures liver tissue. Eventually, the damage causes the liver to release the copper directly into the bloodstream, which carries the copper throughout the body. The copper buildup leads to damage in the kidneys, brain, and eyes. If not treated, Wilson's disease can cause severe brain damage, liver failure, and death.

Symptoms and signs

Symptoms usually appear between the ages of 6 and 20 years, but sometimes not until the age of 30, and in rare instances up to age 50. The most classical sign are the Kayser-Fleischer rings - brown rings around the cornea in the eye - that result from copper deposition in Descemet's membrane of the cornea. Other signs depend on whether the damage occurs in the liver, blood, central nervous system, urinary system, or musculoskeletal system. Many signs would be detected only by a doctor, like swelling of the liver and spleen; fluid buildup in the lining of the abdomen; anemia; low platelet and white blood cell count in the blood; high levels of amino acids, protein, uric acid, and carbohydrates in urine; and softening of the bones. Some symptoms are more obvious, like jaundice, which appears as yellowing of the eyes and skin; vomiting blood; speech and language problems; tremors in the arms and hands; and rigid muscles.

Clinical features

Clinical symptoms rarely develop before 5 years of age, despite the biochemical defect being present at birth. The average concentration of hepatic copper may reach 20 times normal levels, whilst plasma cerulopasmin levels are typically less than 30% of normal.

The age of presentation seems to correlate with the organ system involved. About half (40-50%) of patients first present with hepatic symptoms and half (40-50%) with neurologic symptoms. The average age for hepatic symptoms is 10 to 14 years, compared with 19 to 22 years for neurologic symptoms. Patients rarely present after age 40.

Clinical manifestations

Hepatic

Chronic active hepatitis
Cirrhosis
Fulminant liver failure

Psychiatric

Cognitive impairment
Mood disorder
Psychosis

Neurologic

Ataxia
Dyskinesia
Rigidity
Tremor

Renal

Renal tubular acidosis
Nephrolithiasis

Ophthalmologic

Kayser-Fleischer rings
Sunflower cataracts

Cardiovascular

Cardiomyopathy
Cardiac arrhythmias

Diagnosis

Wilson's disease is diagnosed through tests that measure the amount of copper in the blood, urine, and liver. An eye exam would detect the Kayser-Fleischer ring.

Treatment

The disease is treated with lifelong use of chelating agents such as D-penicillamine or trientine hydrochloride, drugs that help remove copper from tissue. Patients will also need to take vitamin B6 and follow a low-copper diet, which means avoiding mushrooms, nuts, chocolate, dried fruit, liver, and shellfish. Taking extra zinc may be helpful in blocking the intestines' absorption of copper.

Liver transplantation is effective in patients with fulminant Wilson's disease that does not respond to the usual treatment. Because the primary defect resides within the liver, transplantation is curative and the outcome often is excellent.

Wilson's disease requires lifelong treatment. If the disorder is detected early and treated correctly, a person with Wilson's disease can enjoy completely normal health.