Wilson disease is a rare inherited disorder that prevents the body from properly managing copper. This leads to an accumulation of the metal in various tissues, particularly the liver, brain, and eyes. While the body requires a small amount of copper from food, the inability to excrete the excess defines this disease. Without intervention, this progressive condition can result in significant organ damage.
Symptoms of Wilson Disease
Symptoms of Wilson disease often first relate to the liver. Individuals may experience fatigue, jaundice (a yellowing of the skin and eyes), and ascites (fluid buildup in the abdomen). Some people may also notice they bruise or bleed more easily, and over time this can progress to chronic liver disease and cirrhosis.
Neurological issues are also common as copper affects the central nervous system. These manifestations include tremors or shaking in the arms and hands, muscle stiffness, and difficulties with coordination and balance. Speech may become slurred (dysarthria), and swallowing can become challenging.
Psychiatric disturbances are a frequent component of the disease’s presentation. These can include personality changes, depression, anxiety, or mood swings. In some cases, more severe conditions like psychosis can emerge, and these symptoms may be the first signs of the disorder in young adults.
A characteristic sign of Wilson disease is the appearance of Kayser-Fleischer rings. These are golden-brown or greenish rings that form on the outer edge of the cornea, the transparent front part of the eye, caused by copper deposits. While not always present, these rings are a strong indicator of the disease.
The Role of Copper and Genetics
Wilson disease is an autosomal recessive disorder caused by mutations in the ATP7B gene. An individual must inherit a defective copy from both parents to develop the condition. People who inherit only one mutated gene are carriers and do not show symptoms but can pass the gene to their children.
The ATP7B gene provides instructions for a protein that transports copper. In a healthy person, this protein helps the liver excrete excess copper by releasing it into bile, a digestive fluid. This process keeps copper levels balanced.
In Wilson disease, a dysfunctional ATP7B protein prevents the liver from removing copper through bile. Copper then builds up to toxic levels in the liver, causing initial damage. Once the liver’s storage capacity is exceeded, the metal spills into the bloodstream and deposits in other organs like the brain and eyes, causing further symptoms.
Diagnosis Process
Diagnosing Wilson disease involves several tests to measure copper levels. Blood tests check for ceruloplasmin, a protein that carries copper. In most people with the disease, ceruloplasmin levels are low because the liver isn’t producing it correctly.
A 24-hour urine collection is another diagnostic tool. The collected sample is then analyzed to measure the amount of copper being excreted. A high level of copper in the urine is a strong indicator of the disease, as the body attempts to eliminate the excess metal through this alternative pathway.
An eye exam using a slit lamp is performed to look for Kayser-Fleischer rings. A magnified view of the cornea makes it possible to see the copper deposits. The presence of these rings helps confirm the diagnosis.
When other tests are inconclusive, a doctor may recommend a liver biopsy. This procedure involves taking a small sample of liver tissue to measure its copper concentration. Genetic testing can also identify mutations in the ATP7B gene to confirm the diagnosis and identify carriers in the family.
Treatment and Management Strategies
Treatment for Wilson disease is lifelong and focuses on removing excess copper and preventing its re-accumulation. The initial phase involves chelation therapy with medications like penicillamine or trientine. These drugs bind to copper, allowing it to be flushed from the body through urine.
Once copper levels are reduced, treatment shifts to a maintenance phase. Zinc therapy is used for long-term management, as zinc salts block the absorption of copper from food in the digestive tract. This prevents it from entering the bloodstream.
Dietary management is another component of the overall strategy. Patients are advised to avoid foods that are naturally high in copper to complement medical treatments. These foods include:
- Shellfish
- Liver
- Nuts
- Chocolate
- Mushrooms
In cases of severe liver damage leading to acute liver failure or advanced cirrhosis, a liver transplant may be necessary. A transplant is a cure because the new liver has a functional ATP7B gene and can properly process copper. This resolves the underlying metabolic issue.