Wilson's disease (WD) is a rare genetic disorder characterized by copper accumulation in the body. While it typically occurs between the ages of 5 and 45, rare cases have been reported in individuals between the ages of 3 and 63. This disease results from a disruption in copper metabolism.

Copper accumulates in various organs, such as the liver, brain, and eyes, and can cause damage to these organs. If not diagnosed early, it can lead to serious complications such as cirrhosis, liver failure, advanced brain damage, and, unfortunately, death. Therefore, regular screening and early diagnosis are crucial for individuals with a family history of Wilson's disease.

Symptoms of Wilson's disease typically appear between the ages of 6 and 10, but if not diagnosed early, liver and brain symptoms can typically appear in the 20s and 30s. These symptoms can appear in the later stages of the disease due to liver and brain damage.

The prevalence of the disease in the general population can range from 0.3% to 0.7% and is considered a rare disease. Early diagnosis and treatment are crucial for managing the disease's course. Therefore, it is important for people with a family history of Wilson's disease to undergo regular health checkups and necessary screenings.

What is copper and what does it do in our body?

Copper is one of the trace elements our body needs and performs many important functions. We consume approximately 1-2 mg of copper in our daily diet, but our body's daily requirement is approximately 0.75 mg. Copper is absorbed from the food we consume in the small intestines and transported to the liver via the bloodstream. Approximately 90% of excess copper in the body is excreted by the liver along with bile and eliminated from the body through the feces. Approximately 10% of copper is excreted in the urine. When the amount of copper excreted by the liver is insufficient, the body may increase its excretion of copper in the urine; however, this may not be sufficient to completely remove the excess copper from the body.

Copper is essential for a number of vital functions in the body, including healthy connective tissue function, the removal of free radicals from cells, electron transfer, pigment production, and nerve conduction. However, excessive copper accumulation in the body can be harmful and may need to be removed by the body. Disruption of the protein structure or function of the liver's excretion mechanisms, as well as genetic mutations, can lead to the condition known as Wilson's disease. In this condition, copper cannot be regularly excreted and accumulates in the body over time.

What causes Wilson's disease?

Wilson's disease is an autosomal recessive genetic disorder. For this disease to develop, both parents must carry the genetic mutations. In this case, 25% of children will be healthy, while 50% will be carriers and, unfortunately, 25% will develop the disease.

The disease is caused by mutations in the ATP7B gene on chromosome 13. The ATP7B gene encodes the ATPase2 protein, which is responsible for copper excretion in liver cells. Various mutations exist in this gene, and approximately half of these disrupt the structure and function of the ATPase2 protein, preventing it from functioning normally.

The ATPase2 protein allows aposeruloplasmin (the precursor of ceruloplasmin) to bind copper and convert it to ceruloplasmin. Ceruloplasmin is the primary protein that transports copper in the blood. In Wilson's disease, this conversion is inadequate, resulting in decreased ceruloplasmin levels in the blood.

The ATPase2 protein stores copper in liver cells, allowing it to be excreted in the bile ducts and then through bile. However, when ATPase2 activity is deficient, excess copper accumulated in the liver cannot be excreted in bile and accumulates in the cells. In this case, copper can lead to the formation of free radicals in liver cells, causing cell damage.

Liver damage can progress to chronic hepatitis, fulminant hepatitis, and eventually, liver cirrhosis. Accumulated copper can migrate into the intercellular space and bloodstream, where it can be transported to other organs. It can accumulate in the brain and other organs, causing damage in these areas as well. Therefore, Wilson's disease is a genetic disorder that can cause serious damage to various organs, including the liver and brain.

Wilson's disease symptoms

Wilson's disease can present with various symptoms depending on the organs it affects.

• Symptoms of liver damage: Liver involvement due to Wilson's disease is particularly common in children. Early symptoms may be absent, or they may include elevated liver enzymes, fatty liver, fatigue, weakness, loss of appetite, nausea, or abdominal pain. Over time, liver damage can worsen, and symptoms such as jaundice, itching, leg swelling, abdominal fluid accumulation, bleeding, and brain problems due to liver failure can develop. In some cases, a rapidly progressing, severe liver inflammation (fulminant hepatitis) can occur, which can progress to coma. Wilson's disease may also increase the risk of liver cancer.
• Symptoms observed due to accumulation in the brain: Copper accumulation in the brain in Wilson's disease can lead to neurological symptoms. Symptoms such as hand tremors, movement disorders, muscle spasms, lack of coordination, and difficulty swallowing may occur. Psychiatric symptoms can also be observed in 20% of patients, including mood disorders, anxiety, depression, personality changes, antisocial behavior, phobias, compulsive behaviors, dementia, and psychosis.
• Symptoms of eye deposits: Kayser-Fleischer rings may occur due to copper deposits in the eyes. This ring is noted during an eye exam and may be an indicator of Wilson's disease, but it may not be seen in every patient.
• Symptoms in other organs: Wilson's disease can also cause symptoms in other organs. These may include hemolysis (destruction of red blood cells), kidney symptoms, joint symptoms, osteoporosis, heart involvement, endocrinological disorders, and pancreatic involvement.

Wilson's disease is a genetic disorder that can manifest with various symptoms in many parts of the body and cause serious damage to various organs. These symptoms can vary depending on factors such as the severity of the disease, early diagnosis before treatment, and response to treatment. Therefore, the symptoms and severity of the disease can vary from patient to patient.

Who gets Wilson's disease?

Wilson's disease is generally inherited genetically. It can occur in any age group, but those with a known family history are at higher risk. If a family member has been diagnosed with Wilson's disease, it is important to screen other family members for the disease. This screening is particularly important when a new case is discovered. Family screenings can usually begin around age 5. These screenings are crucial for early diagnosis and, if necessary, initiation of treatment. Even if there are no symptoms, screening is recommended for individuals with a known family history.

How is Wilson's disease diagnosed?

A series of tests and examinations are performed to diagnose Wilson's disease. Some of the methods used to diagnose Wilson's disease include:

• Blood tests: Liver function tests are performed. These tests check liver enzyme levels. They also measure copper and ceruloplasmin (a copper-carrying protein). Copper levels are usually high, while ceruloplasmin is low.
• 24-hour urine test: Copper excretion in the urine is measured. People with Wilson's disease may have higher-than-normal copper excretion.
• Eye examination: During an eye exam, an ophthalmologist may observe a ring called a Kayser-Fleischer ring, caused by copper accumulation. This ring is considered a key finding in diagnosing the disease.
• Liver imaging tests: Examination of the liver with ultrasound , computed tomography (CT), or magnetic resonance imaging (MRI) can be helpful in assessing signs of liver disease. These imaging tests can reveal changes such as liver enlargement, spleen enlargement, portal hypertension, or abdominal fluid accumulation.
• Biopsy : A liver biopsy may be performed. During this procedure, tissue taken from the liver can be examined to determine the amount of copper accumulation.

These tests are often used in combination to diagnose WD, and the diagnosis is based on the patient's symptoms and findings. The presence of several of the above-mentioned findings may be sufficient to diagnose Wilson's disease. The diagnostic process often involves combining a series of tests and expert opinions.

How is Wilson's disease treated? Is there a definitive cure for the disease?

Wilson's disease requires specialized treatment, but is manageable when diagnosed early. Treatment focuses on reducing copper accumulation and eliminating it from the body. Treatment methods for Wilson's disease include:

• Low-copper diets: To reduce copper intake and control its absorption, low-copper diets may be recommended. These diets may recommend avoiding or limiting copper-containing foods.
• Medications: Certain medications are used to reduce copper absorption and control its accumulation in the body. Zinc works by reducing copper absorption in the intestines. Medications such as D-penicillamine and trientine are also used to increase copper excretion. While these medications are effective, they can have some side effects and should be used with regular monitoring.
• Chelating agents: Chelating agents are medications that facilitate the excretion of copper from the body. These agents can be excreted by the kidneys and bind to free copper in the circulation. This way, copper accumulation can be reduced by increasing its excretion through urine.
• Liver transplantation: Liver transplantation may be a treatment option for patients with advanced liver disease and complications such as cirrhosis. Liver transplantation is a surgical procedure performed in cases of severe liver damage.

While Wilson's disease is treatable, it cannot be completely eliminated. Early diagnosis and appropriate treatment can prevent or control disease progression. Treatment is determined by the patient's condition, symptoms, and response. Therefore, regular follow-up with a specialist is important.

What should a person with Wilson's disease not eat?

People with Wilson's disease may be advised to avoid or limit certain foods high in copper. This may help prevent further copper accumulation and reduce the effects of the disease. Some copper-rich foods and beverages include:

• Seafood: Seafood such as crab, shrimp, and mussels are rich in copper. Excessive consumption of these foods should be avoided.
• Nuts and seeds: Nuts such as hazelnuts, peanuts, almonds, and walnuts, as well as seeds such as sunflower seeds, sesame seeds, and flaxseeds, are foods high in copper. Consuming these foods excessively can increase copper intake.
• Cocoa and chocolate: Cocoa and chocolate are another food group that contains copper. Dark chocolate, in particular, can be high in copper.
• Drinking water: Some drinking water may contain copper when it passes through copper pipes or systems containing copper. In this case, water with a controlled copper content may be preferred.
• Dried fruits: Dried fruits such as dried apricots, raisins, and dried figs can also be high in copper. Excessive consumption of these should be avoided.

It's important for individuals with Wilson's disease to avoid or limit the consumption of these high-copper foods. However, it's important for individuals to avoid copper-containing foods entirely, establish a balanced diet, or consult with a doctor or nutritionist who specializes in nutrition. This can help maintain copper balance and minimize the effects of the disease.

How does Wilson's disease affect pregnancy?

Wilson's disease is a disorder that can affect hormonal regulation and lead to reproductive problems. Women with liver cirrhosis, in particular, may be at increased risk of infertility. Furthermore, women with this disease may face certain complications and risks during pregnancy.

Medications used to treat Wilson's Disease can affect pregnancy, and therefore patients planning or becoming pregnant should be closely monitored by a healthcare team with expertise in treatment options.

Patients who become pregnant may experience recurrent miscarriages and infertility problems. Therefore, patients with Wilson's disease who are planning or are pregnant should be aware of the risks and health complications that may arise during pregnancy and childbirth. A personalized follow-up program tailored to the specifics of the disease, under the supervision of a specialist physician, is essential.

Women with Wilson's disease should be guided throughout pregnancy by a specialized healthcare team regarding the health risks and treatment plans specific to their condition. This will minimize risks and better protect the health of both mother and baby.