Wilson Disease

What happens in Wilson disease

We absorb copper from food every day. The liver normally removes the excess by attaching it to a carrier protein and passing it into bile, which leaves the body in stool. A protein called ATP7B does this job. In Wilson disease, ATP7B does not work, so copper builds up in liver cells, damaging them. Over time, copper spills into the bloodstream and deposits in the brain (especially the basal ganglia, which control movement), the cornea, the kidneys and red blood cells.

Inheritance

Wilson disease is autosomal recessive: a person must inherit a faulty ATP7B gene from both parents. Parents are usually healthy carriers. Each child of two carriers has a 1 in 4 chance of having the disease. That is why brothers and sisters of anyone diagnosed must be tested.

Wilson disease symptoms

Symptoms vary widely. Some people have only liver disease, some mainly brain symptoms, and some both.

Liver symptoms (often first in children and teens)

• tiredness, poor appetite, abdominal pain
• jaundice (yellow skin and eyes)
• swelling of the legs or belly from fluid
• easy bruising and bleeding
• a picture like hepatitis with no virus found
• cirrhosis found on tests
• sudden acute liver failure, often with hemolytic anemia (breakdown of red blood cells) as copper floods the blood

Neurological symptoms (usually from the late teens onward)

• tremor, including a coarse "wing-beating" tremor of the arms
• stiffness, slowness and other parkinsonian features
• dystonia: abnormal postures and twisting movements
• slurred or slow speech, drooling and trouble swallowing
• clumsiness and deteriorating handwriting
• a fixed, open-mouthed smile

Psychiatric symptoms

• depression, anxiety, irritability and mood swings
• personality change, impulsive or disinhibited behavior
• falling school or work performance
• rarely, psychosis

These can appear years before diagnosis and are often first attributed to adolescence or stress.

Eye and other signs

• Kayser-Fleischer rings: golden-brown rings around the edge of the cornea from copper deposits. Present in nearly all people with brain symptoms, but in only about half of those with liver disease alone. Usually seen with a slit lamp.
• sunflower cataracts
• kidney problems, kidney stones, early osteoporosis and arthritis
• heart rhythm problems and, rarely, menstrual problems or miscarriage

How Wilson disease is diagnosed

No single test is perfect, so doctors combine several:

A scoring system (the Leipzig score) brings these results together. Wilson disease should be considered in anyone between about 3 and 55 with unexplained liver disease, and in young people with movement disorders or unexplained psychiatric symptoms.

Treatment

Treatment is lifelong. Stopping it can lead to rapid, sometimes fatal, liver failure.

Removing copper (chelation)

• Penicillamine binds copper so it is passed in urine. It is effective but has frequent side effects (rash, kidney and blood problems), and can temporarily worsen neurological symptoms early on.
• Trientine works the same way with fewer side effects and is often preferred.

Blocking copper absorption

• Zinc salts block copper absorption from the gut. Zinc is used for maintenance after chelation and for people found by screening before symptoms start.

Diet

During the first year of treatment, avoid foods very high in copper: shellfish, liver and organ meats, nuts, chocolate, mushrooms and dried fruit. Check your drinking water if it comes from a well or copper pipes. Avoid supplements containing copper.

Liver transplant

A transplant is needed for acute liver failure or advanced cirrhosis that does not respond to medicine. It cures the copper problem because the new liver has normal ATP7B.

Monitoring

Regular blood and urine tests check copper levels, liver function, blood counts and kidney function, usually every few months at first and then once or twice a year.

Outlook

When diagnosed early and treated consistently, people with Wilson disease have a near-normal life expectancy. Liver function often improves. Neurological symptoms improve in many people over months to years, but some damage may remain if treatment starts late. Missing doses is the main cause of relapse.

Frequently asked questions

What are the first symptoms of Wilson disease?

In children and teens, the first signs are often liver-related: tiredness, abdominal pain, jaundice or abnormal blood tests. In young adults, early signs can be tremor, slurred speech, clumsiness, mood changes or falling school performance. Some people are found by screening before any symptoms.

Is Wilson disease curable?

It cannot be cured with medicine, but it is very treatable. Lifelong chelation or zinc keeps copper under control and prevents further damage. A liver transplant effectively cures the disease but is reserved for severe liver failure.

What are Kayser-Fleischer rings?

They are golden-brown or greenish rings at the edge of the cornea caused by copper deposits. An eye doctor sees them best with a slit lamp. They are found in almost everyone with neurological Wilson disease and fade with treatment.

Should family members be tested for Wilson disease?

Yes. Brothers and sisters of a person with Wilson disease have a 1 in 4 chance of having it and should be screened with blood, urine and eye tests or genetic testing. Children of an affected person have a much lower risk but are often checked too.

Can diet alone control Wilson disease?

No. Avoiding high-copper foods helps, especially in the first year, but it cannot remove the copper already stored or stop buildup on its own. Medicine is always needed.