What is Wilson's Disease?
Wilson's disease is a rare hereditary disorder that causes copper to accumulate in various organs, primarily the liver, brain, and eyes. Diagnosis typically occurs between the ages of 5 and 35, although younger or older individuals can also be affected.
In a healthy person, copper plays an important role in the formation of nerves, bones, collagen, and melanin, the pigment of the skin. Copper is usually obtained from the foods eaten. Bile is responsible for eliminating excess copper. However, in people with Wilson's disease, copper is not properly eliminated and begins to accumulate in the body. This condition can be life-threatening if not treated. Early diagnosis of Wilson's disease allows for treatment, enabling many individuals to lead a normal life.
Diagnosis Methods for Wilson's Disease
Wilson's disease is not easily diagnosed because the symptoms resemble those of other liver diseases, such as hepatitis. Additionally, the symptoms develop over time, making it difficult to link gradual behavioral changes to Wilson's disease. Diagnosis takes into account not only the symptoms but also test results. The tests and procedures used for diagnosis include:
Blood and Urine Tests
Blood tests can monitor liver functions and check the level of a protein called ceruloplasmin, which binds copper in the blood. The copper level in the blood is also checked with blood tests. Additionally, a 24-hour urine test is conducted to measure the amount of copper excreted in the urine.
Eye Test
In this test, performed by an eye doctor, a slit lamp is used to check for Kayser-Fleischer rings in the eyes. These rings are caused by excess copper in the eyes. Wilson's disease is also associated with a type of cataract called sunflower cataract.
Liver Biopsy
A liver biopsy involves testing a tissue sample from the liver for excess copper.
Genetic Testing
Genetic testing is used to identify the genetic changes that cause Wilson's disease. If someone has the altered gene that causes Wilson's disease, their siblings may also need to be screened. If any sibling has the altered gene, they can start treatment before symptoms begin.
Causes of Wilson's Disease
Wilson's disease is caused by mutations in the ATP7B gene, which is responsible for eliminating excess copper from the body. The mutation is inherited from the parents. To develop Wilson's disease, a person must inherit one abnormal gene from each parent. Having one mutated gene does not cause the disease but makes the person a carrier, meaning they can pass the gene to their children.
Symptoms of Wilson's Disease
The symptoms of Wilson's disease vary significantly from person to person. While the disease is present from birth, symptoms do not appear until copper accumulates in the liver, brain, eyes, or other organs. Symptoms usually develop between the ages of 5 and 40, but they can occur later or earlier. Because the symptoms are so diverse, individuals with Wilson's disease may be misdiagnosed with other liver or mental health disorders until copper levels are measured.
Liver Symptoms
People with Wilson's disease often exhibit symptoms of hepatitis and may develop acute liver failure due to sudden declines in liver function. Symptoms may include:
- Fatigue
- Jaundice
- Nausea
- Vomiting
- Pale stools
- Loss of appetite
- Dark urine
- Abdominal pain
Some individuals with Wilson's disease develop chronic liver disease and cirrhosis complications, resulting in symptoms such as:
- Fatigue and weakness
- Severe jaundice
- Unexpected weight loss
- Itching
- Fluid accumulation in the abdomen
- Swelling in the lower legs, ankles, or feet
Central Nervous System Symptoms
Individuals with Wilson's disease may develop central nervous system symptoms affecting mental health due to copper accumulation in the body. These symptoms are more common in adults but can also occur in children. Symptoms affecting the nervous system include:
- Problems with speech, swallowing, or physical coordination
- Muscle stiffness
- Tremors or uncontrolled movements
When mental health is affected, symptoms may include:
- Anxiety
- Changes in mood, personality, or behavior
- Depression
- Disturbances in thoughts and feelings that make it difficult to differentiate reality from non-reality
Eye Symptoms
Many individuals with Wilson's disease have green, golden, or brown rings around the edges of their corneas, known as Kayser-Fleischer rings. These rings result from copper accumulation in the eyes, diagnosed using a slit-lamp examination.
Kayser-Fleischer rings are present in a significant portion of individuals whose nervous system is affected by Wilson's disease. About half of the people diagnosed with Wilson's disease, who only have liver symptoms, also have these rings.
Other Symptoms of Wilson's Disease
Wilson's disease can also affect other parts of the body, leading to symptoms such as:
- Hemolytic anemia
- Bone and joint problems
- Heart problems
- Kidney problems
Treatment Methods for Wilson's Disease
The treatment of Wilson's disease aims to reduce toxic levels of copper in the body and prevent organ damage. Treatment includes:
- Medications that help remove copper from the body
- Zinc to prevent copper absorption in the intestines
- A diet low in copper
Patients with Wilson's disease require lifelong treatment. Stopping treatment can lead to acute liver failure. Doctors regularly perform blood and urine tests to monitor the effectiveness of the treatment.
Medication for Wilson's Disease
Several different medications are recommended to reduce excess copper in the body. These include:
Chelating Agents
Chelating agents help remove copper from the body and include:
- Penicillamine
- Trientine
Doctors gradually increase the dose of these medications from the start of treatment. Patients take high doses of chelating agents until the excess copper is eliminated. When symptoms improve and tests show that copper levels are safe, doctors prescribe lower doses of chelating agents as maintenance treatment. Lifelong use of chelating agents prevents the reaccumulation of copper. These agents may have some side effects, and patients should check with their doctor about the need for supplements like vitamins before surgery.
Zinc
Zinc prevents the intestines from absorbing copper. It can be prescribed as maintenance therapy after removing excess copper from the body with chelating agents. Zinc can also be prescribed for those with Wilson's disease who do not yet have symptoms.
Treatment for Pregnant Women
Pregnant women with Wilson's disease should discuss their treatment plan with their doctor. Since the fetus needs a small amount of copper, the doctor may prescribe lower doses of chelating agents. Having an obstetrician familiar with Wilson's disease is crucial. Patients should also discuss with their doctor whether it is safe to breastfeed while undergoing treatment for Wilson's disease.
Surgery (Transplant) for Wilson's Disease
Wilson's disease can cause acute liver failure or gradually lead to liver failure. If the liver damage is irreversible, a liver transplant may be necessary. The donor organ for a liver transplant can come from a living donor or a recently deceased donor. In the case of a living donor, part of the liver is used, whereas the entire liver is used from a recently deceased donor.
Surgical Methods for Wilson's Disease
Liver surgeries are called hepatectomies. These technically challenging surgeries involve many blood vessels in the liver. Surgeons use special techniques to prevent bleeding, as individuals with liver failure are more prone to bleeding due to the liver's inability to produce clotting factors. Liver transplant surgeries, which can last between 6 and 12 hours, require significant blood transfusions. After the surgery, patients need to be monitored for at least 24 hours. The hospital stay typically lasts 1 to 3 weeks.
Liver transplants are major surgeries performed under general anesthesia. Various tubes are placed in the body to assist with specific functions during and after surgery. These tubes include:
- Intravenous catheters in the arm or hand for administering fluids and medications
- Intravenous catheters in the neck or groin vein for monitoring blood pressure and taking blood samples
- A tube attached to a mechanical ventilator, inserted through the mouth into the windpipe
- Tubes placed in the abdomen to drain blood and fluids around the liver
- A nasogastric tube inserted through the nose into the stomach to drain stomach secretions
- A catheter placed in the bladder to drain urine
After placing the necessary tubes, the surgeon makes a long incision in the abdomen to access the liver. The liver is carefully separated, and the blood vessels and bile ducts are clamped. The new liver is then placed, and the blood vessels and bile ducts are connected. After closing the incision, patients are moved to intensive care.
Side Effects of Wilson's Disease Surgery
The main risks associated with liver transplant procedures include:
Blood Clots
The risk of blood clotting increases due to the lengthy duration of liver transplant surgeries. Generally, this risk is below 5%.
Bleeding
Due to clotting disorders caused by liver damage, there is significant bleeding during the surgery. Surgeons frequently use automated blood transfusion technology to manage this.
Bile Duct Injury
Injury during surgery can cause bile to leak into the abdominal cavity, which is toxic to the body. Scar tissue may develop at the injury site after surgery, or narrowing or blockage may occur, preventing bile from flowing back into the liver.
Liver Failure
In some cases, the donor liver may be damaged during transplantation and fail to function post-surgery. If this occurs, a new donor is needed as soon as possible. This situation occurs in about 5% of cases.
Benefits of Wilson's Disease Surgery
When Wilson's disease causes irreversible liver damage, a liver transplant is the only option for patients to continue living. Therefore, liver transplants are crucial for these patients.
Complications of Wilson's Disease Surgery
The most significant complications of liver transplantation are organ rejection and infection.
Organ Rejection
Although doctors use immunosuppressive medications to prevent the immune system from attacking the new liver, mild rejection episodes frequently occur in the first year after transplantation. Acute organ rejection occurs in 25% to 50% of liver transplant recipients within the first year. The highest risk of organ rejection is in the first 4 to 6 weeks after transplantation.
The first evidence of acute organ rejection is usually elevated liver enzymes in blood tests. A liver biopsy confirms the diagnosis, and treatment continues with adjusted immunosuppressive medications. About 5% of patients may experience chronic organ rejection, with recurrent attacks despite medication. Chronic organ rejection can eventually lead to the failure of the new liver.
Infection
All surgical procedures carry some risk of infection, but this risk is much higher with organ transplantation. The use of immunosuppressive medications after organ transplantation increases the risk of infection as a side effect. These medications weaken the immune system, preventing it from effectively fighting infections. Post-discharge infections, as well as hospital-acquired infections, fall into this category.
Bacterial and fungal infections are common in the first months after surgery when the dose of immunosuppressive medications is highest. Various viral infections can occur within the first 6 months. Patients may need to take extra precautions to protect themselves, especially in the first 6 months after surgery. If an infection occurs, doctors may recommend antibiotic treatment.
Long-term complications of liver transplantation include:
- Hypertension
- High blood sugar and type 2 diabetes
- Kidney disease
- Kidney failure
- Cancer risk
Life After Wilson's Disease Surgery
Patients may need to stay in the intensive care unit for a few days after surgery. During this time, the healthcare team will monitor the patient's condition and watch for signs of complications. Various blood samples will be taken to check how the new liver is functioning. Fluid and electrolyte balance, blood sugar levels, and blood volume may need to be actively managed through IV.
Once the patient's condition stabilizes, the tubes are removed, and the patient is transferred to a regular hospital room for a 1 to 3-week stay. It may take a few days for the intestines to start working again. Patients initially consume fluids and gradually transition to solid foods. Pain medication is gradually reduced before discharge.
After discharge, patients must frequently visit for follow-up appointments. Regular blood tests will continue to monitor the new liver's condition. Stitches may be removed after a few weeks. Various medications are prescribed immediately after surgery, some of which are continued for life.
Recovery Process for Wilson's Disease
Treatment for Wilson's disease is lifelong. The timeline for when patients will start feeling better depends on the severity of their symptoms. However, symptoms significantly decrease after 4 to 6 months of treatment and regular maintenance therapy. Regular testing by a healthcare professional is necessary to determine the success of Wilson's disease treatment.
Precautions for Wilson's Disease Patients
It is crucial for individuals with Wilson's disease to take their medications as prescribed by their doctor. Foods high in copper should also be eliminated from their diet. Treatment can reduce symptoms and prevent life-threatening complications.
If symptoms worsen after initially improving with treatment, a doctor should be consulted, as this may indicate a need to adjust medication dosages.
If symptoms prevent maintaining a normal routine, especially if eating is problematic, vomiting is persistent, or jaundice occurs, immediate medical attention should be sought.
Diet for Wilson's Disease
Individuals with Wilson's disease should avoid foods high in copper. Foods high in copper include:
- Shellfish
- Liver
- Chocolate
- Dried fruits
- Dried beans
- Peas
- Mushrooms
- Nuts
After reducing copper levels in the body and starting maintenance therapy, some of these foods can be consumed in reasonable amounts.
Individuals using tap water should check if their plumbing contains copper pipes. A water filter is recommended to make water from copper pipes safe to drink.
