Copper is an essential trace mineral, a vital nutrient that our bodies need in small amounts to help nerves function, form strong connective tissue, and produce energy. In a healthy person, the body skillfully balances the amount of copper it absorbs from food with the amount it excretes. But what if this delicate balancing act fails? In a rare genetic disorder known as Wilson disease, a faulty gene disrupts this process, causing copper to accumulate to toxic levels, primarily in the liver and the brain. If left undiagnosed and untreated, this copper overload can lead to devastating liver disease, severe neurological problems, and is ultimately fatal. However, Wilson disease is also a remarkable story of medical progress. With early diagnosis and a commitment to lifelong treatment, the toxic copper can be removed. Individuals with this condition can live full, healthy, and normal lives.

Wilson disease is an inherited disorder of copper metabolism. The core problem lies in the body’s inability to excrete excess copper. Our bodies get copper from the foods we eat, like shellfish, nuts and chocolate. The liver plays the central role in managing this copper. It takes up copper from the bloodstream, uses what is needed, and, most importantly, gets rid of any surplus by excreting it into bile. Bile is a digestive fluid that flows into the intestines. The copper within it is then eliminated from the body in the stool.

To understand Wilson disease, it is helpful to use an analogy. Think of your liver as a sophisticated “copper management facility.” It is the only place in the body with the machinery to package and export excess copper. A specific protein in the liver acts as the “shipping manager.” Its job is to load excess copper onto “garbage trucks” (another protein called ceruloplasmin) and send it out for disposal via the bile ducts.

In Wilson disease, this “shipping manager” protein is broken due to a genetic defect. It cannot properly load copper for excretion. This leads to two major problems:

1. Copper begins to accumulate to toxic levels inside the liver cells, causing progressive liver damage, inflammation (hepatitis), and scarring (cirrhosis).
2. Once the liver’s storage capacity is overwhelmed, the toxic copper spills out of the liver and into the bloodstream. From there, it travels throughout the body and deposits in other organs, most notably the brain (causing neurological and psychiatric symptoms) and the eyes.

In my experience, Wilson Disease is often missed in teens or young adults with unexplained liver or psychiatric issues. If there’s even mild liver enzyme elevation or personality change, it’s worth ruling out this treatable condition.

Wilson disease is caused by mutation in the ATP7B gene. This gene, located on chromosome 13, contains the precise set of genetic instructions for making a protein called the copper-transporting ATPase 2.

This ATP7B protein is the “shipping manager” from our analogy. It is a vital transporter protein located within the liver cells, and it has two critical functions:

1. It helps to incorporate copper into a protein called apoceruloplasmin, creating the final ceruloplasmin protein that can safely transport copper in the blood.
2. It is responsible for collecting excess copper within the liver cell and transporting it into the bile for excretion from the body.

When the ATP7B gene is mutated, a faulty or non-functional protein is produced. This broken transporter cannot perform its essential duties. As a result, copper cannot be properly loaded onto ceruloplasmin (leading to low levels of ceruloplasmin in the blood), and more importantly, it cannot be excreted into the bile. This leads to the toxic, progressive accumulation of copper in the body that defines Wilson disease.

When I see liver damage in a young adult without a history of alcohol, hepatitis, or drug use, I strongly suspect Wilson Disease. The key is catching it before irreversible damage occurs.

Wilson Disease is not contagious and inherited in an autosomal recessive pattern. This means:

• For a child to have the disease, they must inherit two copies of the mutated ATP7B gene, one from their mother and one from their father.
• Parents are almost always unaffected carriers. A carrier has one normal copy of the gene and one mutated copy. Their one normal gene produces enough of the functional protein to prevent them from developing the disease, so they are typically unaware they carry the gene.

When two carriers have a child, there are three possible outcomes for each and every pregnancy:

• There is a 25% chance that the child will inherit a mutated gene from both parents and will be affected with Wilson disease.
• There is a 50% chance that the child will inherit one mutated gene and one normal gene and will be an unaffected carrier, just like the parents.
• There is a 25% chance that the child will inherit two normal genes and will be neither affected nor a carrier.

Because both parents must carry the same rare faulty gene, the chances of having a child with an autosomal recessive condition like Wilson disease are higher in communities where marriage between close relatives, such as first cousins, is a common cultural practice. This is because related individuals have a greater likelihood of carrying the same inherited genetic traits.

I’ve often had patients discover they had Wilson Disease only after a sibling was diagnosed. It’s a reminder of how critical family screening is, especially when the condition is so manageable if caught early.

Wilson Disease can present with a wide range of symptoms depending on which organs are affected and the patient’s age. Symptoms typically appear between ages 5 and 35, but they can start at any age. The symptoms are generally grouped into those affecting the liver, the brain, and the eyes.

Hepatic (Liver-Related) Symptoms

Liver problems are often the first sign of Wilson disease, especially in children and teenagers. The presentation can range from mild to life-threatening.

• Fatigue and weakness.
• Jaundice (yellowing of the skin and whites of the eyes).
• Abdominal pain or a feeling of fullness due to an enlarged liver or spleen.
• Fluid buildup in the abdomen (ascites) or swelling in the legs (edema).
• Easy bruising and prolonged bleeding.
• Some individuals can present with acute liver failure, a sudden and severe illness that is a medical emergency.

Neurological Symptoms

Neurological symptoms are more common to appear in late adolescence and young adulthood as copper begins to accumulate in the brain. They often affect movement and coordination.

• Clumsiness and a decline in academic or work performance.
• Tremors, especially a characteristic “wing-beating” tremor of the arms.
• Difficulty speaking (dysarthria), with slurred speech.
• Difficulty swallowing (dysphagia).
• A fixed, “mask-like” facial expression or unusual smiling.
• Poor coordination and an unsteady gait.
• Muscle stiffness and dystonia (sustained muscle contractions).

Psychiatric Symptoms

The buildup of copper in the brain can also cause significant psychiatric problems, which can be the very first sign of the disease and are often misdiagnosed.

• Depression or anxiety.
• Personality changes, like irritability, impulsivity or mood swings.
• In some cases, psychosis with delusions or hallucinations.

Ocular (Eye) Sign

• Kayser-Fleischer Rings: This is the hallmark and most famous sign of Wilson disease. They are golden-brown, greenish, or coppery-colored rings that appear on the outer edge of the cornea (the clear part of the eye). They are caused by copper deposits and are visible only during a specialized eye exam called a slit-lamp exam.

I’ve often seen subtle mood changes or academic decline as the first signs in teens. When these come with unexplained liver findings or tremors, Wilson Disease should always be on the differential.

Diagnosis of Wilson Disease involves clinical evaluation, blood and urine tests, imaging, and sometimes genetic testing.

1. Blood Tests:
   • Serum Ceruloplasmin: This is the most important initial screening test. In about 90% of people with Wilson disease, the level of this copper-carrying protein will be low.
   • Serum Copper: This test can be misleading. While total copper may be low, the level of “free” copper not bound to ceruloplasmin is actually high.
2. 24-Hour Urine Copper Excretion: This is a key diagnostic test. The patient collects all of their urine over a 24-hour period. In a person with Wilson disease, the amount of copper being excreted in the urine will be abnormally high.
3. Slit-Lamp Eye Exam: An ophthalmologist will perform this specialized exam to look for the presence of Kayser-Fleischer rings.
4. Liver Biopsy: Historically considered the gold standard, a liver biopsy may be performed if other tests are inconclusive. A small sample of liver tissue is removed with a needle and is analyzed to measure the concentration of copper directly.
5. Genetic Testing: A blood test can be done to look for mutations in the ATP7B gene. This can confirm the diagnosis and is essential for screening the patient’s siblings, who have a 25% chance of also having the disease.

When lab results show low ceruloplasmin and high urinary copper in a young patient with liver issues, I push for a liver biopsy or genetic test. Getting the diagnosis early can literally change a life’s trajectory.

Wilson Disease is 100% treatable. It requires lifelong treatment to prevent copper accumulation and organ damage. With proper therapy, most people can lead normal, healthy lives.

1. Initial Treatment: Chelation Therapy

The first phase of treatment involves using drugs called chelators. These are drugs that bind to copper in the tissues and bloodstream, forming a compound that can then be excreted from the body through the urine.

• Penicillamine: One of the original treatments for Wilson disease.
• Trientine: Another effective chelating agent, often with fewer side effects than penicillamine.

2. Maintenance Therapy

Once the excess copper has been removed and symptoms have improved, the patient will transition to a lifelong maintenance therapy to prevent copper from re-accumulating.

• Zinc Salts: This is a very common and effective maintenance therapy. Zinc works by blocking copper absorption from the diet in the intestines. It stimulates the production of a protein in the intestinal cells that traps copper and prevents it from entering the bloodstream.

3. Dietary Management

During the initial phase of treatment, patients are advised to follow a low-copper diet. This means avoiding foods that are very high in copper, such as:

• Shellfish
• Liver
• Nuts and seeds
• Chocolate
• Mushrooms

Patients may also be advised to test their home water supply if they have copper pipes.

4. Liver Transplant

For individuals who are diagnosed very late and present with acute liver failure or end-stage cirrhosis, a liver transplant is a life-saving and curative option. The new, healthy liver has a normal ATP7B gene and can properly manage copper, curing the disease.

With consistent chelation and lifestyle changes, I’ve seen patients with severe early symptoms bounce back incredibly well. The key is strict adherence to treatment and routine follow-ups.

Wilson Disease is a rare genetic disorder that turns an essential mineral into a potent poison. Its slow, insidious buildup of copper can lead to devastating liver failure and irreversible neurological damage if it is not recognized. The disease can mimic many other conditions, from chronic liver disease to psychiatric disorders, making diagnosis a significant challenge. However, Wilson Disease stands as a powerful example of a treatable metabolic condition. With a high index of suspicion, a definitive diagnosis can be made through straightforward tests. A commitment to lifelong chelation or zinc therapy can remove the toxic copper and prevent its reaccumulation, allowing individuals to halt the progression of the disease and live completely normal, healthy lives.

1. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). (2021). Wilson Disease. Retrieved from https://www.niddk.nih.gov/health-information/liver-disease/wilson-disease
2. National Organization for Rare Disorders (NORD). (2023). Wilson Disease. Retrieved from https://rarediseases.org/rare-diseases/wilson-disease/
3. Wilson Disease Association. (n.d.). About Wilson Disease. Retrieved from https://www.wilsonsdisease.org/for-patients-families/about-wilson-disease