Hepatolenticular degeneration

Definition

Wilson's disease is an inherited disorder where there is excessive amounts of copper in the body's tissues. This causes a variety of effects, including liver disease

Alternative Names

Causes

Wilson's disease is a rare inherited disorder. If both parents carry an abnormal gene for Wilson's disease, there is a 25% chance in each pregnancy that the child will have the disorder (i.e., it is an autosomal recessive disease).

Wilson's disease causes the body to take in and keep too much copper. The copper deposits in the liver, brain, kidneys, and the eyes. The deposits of copper cause tissue damage, death of the tissues, and scarring, which causes the affected organs to stop working correctly. Liver failure and damage to the central nervous system (brain, spinal cord) are the most predominant, and the most dangerous, effects of the disorder. If not caught and treated early, Wilson's disease is fatal.

It is most common in eastern Europeans, Sicilians, and southern Italians, but may occur in any group. The disorder most commonly appears in people under 40 years old. In children, the symptoms begin to show by around 4 years of age.

Symptoms

• Enlargement of the abdomen (abdominal distention)
• Splenomegaly
• Yellow skin (jaundice) or yellow color of the white of the eye (icterus)
• Vomiting blood
• Weakness
• Tremors of the arms or hands
• Difficulty moving arms and legs, stiffness
• Abnormal arms and legs posture
• Slow movements
• Difficulty walking
• Unpredictable and jerky movement
• Uncontrollable movement
• Weakness of the head, neck, face, or arms
• Speech impairment
• Slow or decreased facial movement and expressions
• Emotional or behavioral changes
• Confusion or delirium
• Dementia (loss of many brain functions)

Exams and Tests

An eye examination may show:

• Kayser-Fleischer rings (rusty or brown-colored ring around the iris).
• Eye movement may be restricted.

A physical examination may show signs of:

• Liver or spleen disorders (including cirrhosis and liver necrosis)
• Damage to the central nervous system including loss of coordination, loss of muscle control, muscle tremors, loss of cognitive and intellectual functions, loss of memory, confusion (delirium or dementia), and other damage.

Lab findings may include:

• Serum ceruloplasmin - low (although it is normal in 5% of cases)
• Serum copper - low in spite of the copper deposits in tissues
• Urine copper - high
• CBC - may show hemolytic anemia or decreased white blood cell count
• Serum uric acid levels - low

If there are liver problems, lab abnormalities include:

• PT and PTT - elevated
• AST and ALT - elevated
• Albumin - decreased
• Bilirubin - elevated

Other tests findings may include:

• Head MRI or head CT scan may be abnormal, especially in a region of the brain called the basal ganglia.
• Abdominal x-ray, abdominal MRI, or CT scan of the abdomen may indicate liver disease or other abnormality.
• Liver biopsy or biopsy of the kidneys or other suspect tissue shows deposits of copper, and shows tissue changes that indicate damage to the tissues. This disease may increase the protein and amino acid levels in a 24-hr. urine specimen.

The specific gene responsible for the abnormality that causes Wilson's disease has been identified. It is called ATP7B. However, a simple genetic test to screen for Wilson's disease has not yet been developed. Testing is complicated because there are many possible mutations in this gene.

Treatment

The goals of treatment are to reduce the amount of copper in the tissues and to manage the symptoms of the disorder. Treatment must be lifelong.

The following medications may be used:

• Zinc acetate (Galzin), which blocks the absorption (taking in) of copper in the intestinal tract.
• Trientine (Syprine), which binds (chelates) the copper and leads to increased release of the copper through the urine.
• Penicillamine (Cuprimine, Depen), which also binds copper and leads to increased urinary release of copper.

Sometimes, medications that chelate copper, especially penicillamine, can worsen the person's neurological function. There are other medications under investigation which will, hopefully, bind copper without risking possible worsening of neurological function.

In addition, a low-copper diet may be recommended, including avoiding mushrooms, nuts, chocolate, dried fruit, liver, and shellfish. Distilled water may be suggested because most tap water flows through copper pipes. Patients are advised to avoid using copper cooking utensils.

Symptoms are treated as appropriate, including exercises or physical therapy, and protective measures for people who are confused or unable to care for themselves.

In cases where the liver is severely damaged by the disease, liver transplantation might be considered by healthcare providers.

Support Groups

Wilson disease support groups can be found at www.wilsonsdisease.org and www.geneticalliance.org.

Outlook (Prognosis)

Lifelong treatment is required to control the disorder. The disorder may cause fatal effects, especially loss of liver function and toxic effects of copper on the nervous system. In cases where the disorder is not fatal, symptoms may be disabling.

Possible Complications

• Hepatitis
• Cirrhosis
• Death of liver tissues
• Spleen dysfunction
• Anemia
• Increased number of infections
• Injury caused by falls
• Loss of ability to interact with other people
• Loss of ability to function at work and home
• Loss of ability to care for self
• Loss of muscle mass (muscle atrophy)
• Joint contractures or other deformity
• Increased number of bone fractures
• Side effects of penicillamine
• Side effects of other medications used to treat the disorder

When to Contact a Medical Professional

Call your health care provider if symptoms indicate Wilson's disease may be present. Call a genetic counselor if Wilson's disease is present in your family and you are planning to have children.

Prevention

Genetic counseling is recommended for persons with a family history of Wilson's disease.