Hepato-lenticular Degeneration (Wilson Disease)

Hepato-lenticular degeneration, also known as Wilson disease, is a rare inherited disorder where the body cannot properly eliminate copper, leading to its dangerous accumulation in the liver, brain, and other organs. While this condition can be life-threatening if untreated, early diagnosis and lifelong management can allow most people to live normal, healthy lives.

Table of contents

• What is Hepato-lenticular Degeneration?
• Causes and Inheritance
• Signs and Symptoms
• Organs Affected by Copper Accumulation
• How the Disease is Diagnosed
• Treatment Options
• Outlook and Living with the Condition

Wilson disease, Wilson’s disease, hepatolenticular degeneration, progressive lenticular degeneration, copper storage disease

E83.0
277900
D006527
10019819

• Liver
• Brain (particularly basal ganglia, putamen, and pallidum)
• Cornea
• Kidneys
• Heart
• Bones

What is Hepato-lenticular Degeneration?

Hepato-lenticular degeneration, more commonly called Wilson disease, is a rare genetic disorder that prevents the body from properly processing and eliminating copper^[1]. While copper is an essential mineral that we all need in small amounts from our diet, too much copper becomes poisonous to the body. In healthy individuals, the liver filters out excess copper and releases it through bile into the intestines, where it is eventually excreted^[3].

In people with this condition, the normal copper removal process does not work correctly. Instead of being eliminated, excess copper builds up first in the liver and eventually spills into the bloodstream, where it deposits in other organs including the brain, eyes, kidneys, and heart^[1]. This accumulation begins at birth, but symptoms typically do not appear until copper levels have built up significantly over years^[2].

The condition affects approximately 1 in 30,000 people worldwide, though it may be more common in isolated populations^[6]. Most people with Wilson disease are diagnosed between the ages of 5 and 35, though younger and older individuals can also be affected^[2].

Causes and Inheritance

Wilson disease is caused by mutations in a gene called ATP7B, which provides instructions for making a protein that transports copper within cells^[1]. This protein is especially important in liver cells, where it helps package excess copper into bile for elimination from the body. When the ATP7B gene is faulty, this copper transport system does not work properly, leading to toxic copper accumulation.

The condition is inherited in an autosomal recessive manner^[1]. This means that for a person to develop Wilson disease, they must inherit two copies of the faulty gene—one from each parent. If both parents carry one faulty copy of the gene, each child has a one in four chance of inheriting both faulty genes and developing the disease^[16]. People who inherit only one faulty gene are called carriers and typically do not develop symptoms, but they can pass the gene to their children.

Most people with Wilson disease have no family history of the disorder^[6]. However, if you have a parent or sibling with Wilson disease, you are at increased risk and may benefit from genetic testing to determine if you are a carrier.

Signs and Symptoms

The signs and symptoms of Wilson disease vary widely depending on which organs are affected by copper accumulation and at what age symptoms begin^[1]. The condition is present at birth, but symptoms do not appear until copper levels have built up significantly, which usually takes several years^[2].

Generally, children tend to develop liver-related symptoms first, often appearing in the first decade of life. Neurological and psychiatric symptoms typically appear later, usually in the third or fourth decades of life^[1]. However, this pattern can vary considerably between individuals, even within the same family^[6].

Liver-related symptoms may include tiredness, loss of appetite, yellowing of the skin and eyes (called jaundice), fluid buildup in the legs or abdomen, itching, nausea, vomiting, and abdominal pain or swelling^[2]. Some people develop severe liver inflammation or even acute liver failure^[1].

When copper accumulates in the brain, it can cause problems with movement and coordination, tremors, muscle stiffness, difficulty with speech or swallowing, and slowed or jerky movements^[1]. People may also experience changes in mood or personality, depression, anxiety, difficulty sleeping, and in some cases, hallucinations^[1].

A characteristic sign of Wilson disease is the presence of Kayser-Fleischer rings—golden-brown or copper-colored rings around the edges of the cornea in the eyes^[2]. These rings are caused by copper deposits and are visible during an eye examination with a special light. They are present in most people with neurological symptoms but may not be visible in those with only liver disease^[6].

Organs Affected by Copper Accumulation

While the liver and brain are the primary organs affected in hepato-lenticular degeneration, copper accumulation can damage several other body systems^[1].

The liver is always affected first because it is the main organ responsible for processing copper. Over time, copper buildup causes inflammation and scarring of liver tissue, a condition called cirrhosis. In some cases, this can progress to liver failure^[4]. Around half of people with Wilson disease have symptoms limited to the liver^[3].

In the brain, copper deposits particularly affect structures called the basal ganglia, including areas known as the putamen and pallidum^[3]. These brain regions control movement and coordination, which explains why people develop tremors, stiffness, and difficulty with coordinated movements. The damage to these brain structures appears to be irreversible, meaning that movement problems may persist even after treatment begins^[3].

The kidneys can also be affected, particularly the filtering tubes within them. This can lead to problems with kidney function and the appearance of protein or blood in the urine^[1]. The heart may develop a condition called cardiomyopathy, where the heart muscle becomes weakened^[1]. Copper accumulation in bones can cause joint pain and a bone-thinning condition called osteoporosis^[6].

How the Disease is Diagnosed

Diagnosing Wilson disease can be challenging because its symptoms are similar to many other liver and neurological conditions^[6]. Doctors typically use a combination of different tests to confirm the diagnosis.

Blood tests are usually performed first. These include measuring the level of a protein called ceruloplasmin, which normally carries copper in the blood. Most people with Wilson disease have low ceruloplasmin levels^[1]. Blood tests can also measure copper levels, though these may be elevated or normal depending on the stage of disease.

A 24-hour urine collection test measures how much copper is being eliminated in the urine. People with Wilson disease typically excrete much higher amounts of copper than normal^[6].

An eye examination using a special light called a slit-lamp can detect Kayser-Fleischer rings in the cornea^[1]. The presence of these rings strongly suggests Wilson disease, especially when combined with other abnormal test results.

In some cases, a liver biopsy may be performed, where a small tissue sample is removed from the liver and analyzed in a laboratory. This test can measure the amount of copper stored in liver tissue, which is usually very high in people with Wilson disease^[1].

Genetic testing can identify mutations in the ATP7B gene and confirm the diagnosis. This testing is particularly useful for screening family members of people with Wilson disease to determine if they are carriers or at risk of developing the condition^[1].

Treatment Options

While there is currently no cure for Wilson disease, the condition can be effectively managed with lifelong treatment^[2]. The main goals of treatment are to remove excess copper from the body and prevent further accumulation. With proper treatment started early, most people with Wilson disease can live normal, healthy lives^[2].

Medications called chelating agents work by binding to copper in the body and helping to remove it through urine. The most commonly used chelating agents are D-penicillamine and trientine^[1]. These medications are typically taken for life and can be very effective at reducing copper levels. Another medication under investigation is tetrathiomolybdate, which may be particularly useful for people with neurological symptoms^[12].

Zinc supplements are another important treatment option. Zinc works differently from chelating agents—instead of removing copper already in the body, it blocks the absorption of copper from food in the intestines^[1]. Zinc can be used alone in people who do not yet have symptoms or in combination with chelating agents.

Dietary changes are an important part of managing Wilson disease, especially in the first year after diagnosis. People with the condition should avoid foods that are very high in copper, including organ meats (such as liver), shellfish (such as oysters, lobster, and crab), mushrooms, nuts, chocolate, and dried beans^[5]. It is also important to have your drinking water tested for copper content, especially if you have copper plumbing in your home.

In severe cases where the liver is severely damaged or failing, or when medications are not effective, a liver transplant may be necessary^[1]. A liver transplant can be life-saving and may cure the metabolic problem since the new liver can properly eliminate copper.

Treatment must be continued throughout life, even if symptoms improve or disappear. Stopping treatment can lead to dangerous copper accumulation and potentially fatal complications^[6].

Outlook and Living with the Condition

The outlook for people with Wilson disease depends largely on how early the condition is diagnosed and how quickly treatment is started. If left untreated, Wilson disease is invariably fatal, particularly due to acute liver failure^[1].

However, when diagnosed early and properly treated, the prognosis is generally good^[2]. Most people can live normal lives with appropriate medication and dietary management. Liver damage can often be stabilized, and in some cases, even severe neurological disability can be reversed with treatment^[12].

It is important to note that some damage, particularly to the brain, may be permanent if significant copper accumulation has already occurred before treatment begins^[3]. This is why early detection is so critical.

People with Wilson disease need lifelong monitoring by healthcare professionals, including regular blood tests to check copper levels and assess liver and kidney function. Medication doses may need to be adjusted over time. If you have Wilson disease, it is important never to stop your medication without discussing it with your doctor, even if you feel well.

Family screening is also important. If you have been diagnosed with Wilson disease, your siblings and children should be tested, as they may have inherited the same genetic mutations^[6]. Early detection in family members can allow treatment to begin before symptoms develop, preventing organ damage entirely.