Wilson Disease

Wilson disease is a rare inherited disorder in which excess copper is abnormally stored in various tissues in the body, most commonly the liver, brain and corneas of the eyes. While the disorder can begin affecting liver function as early as 6 years of age, most clinical symptoms – including yellowing of skin, swelling in the legs, prolonged bleeding and fatigue – don’t typically appear until the teens or early twenties. Most people with Wilson disease are diagnosed between the ages of 5 and 35. In some cases, screening blood test in childhood reveal signs of liver injury, leading to a diagnosis before symptoms occur.

If left untreated, Wilson disease can cause progressive liver disease, central nervous system dysfunction and death. Early diagnosis and treatment will prevent these long-term and potentially life-threatening complications. Treatment is geared toward removing the overload of copper in the body, then in maintaining normal copper levels.

Wilson disease is believed to affect one in 30,000 to 40,000 people in worldwide, affecting males and females in equal numbers, and affecting all races and ethnic groups. More than 2,000 people have been diagnosed with the disorder in the United States.

Symptoms of Wilson disease vary among individuals, over time and may include liver, neurologic or psychiatric-based features such as:

• Jaundice, a yellow discoloration of the skin, mucous membranes and eyes
• Swelling – particularly in the legs and abdomen – due to abnormal fluid retention
• Increased bruising and bleeding
• Fatigue
• Difficulty speaking clearly
• Psychiatric problems

Clinical signs of Wilson disease also vary and may include:

• Elevated liver enzymes
• High copper levels in the blood
• Low ceruloplasmin level in the blood
• Kayser-Fleisher rings (brown deposits in the corneas of the eyes
• Copper deposits in the liver, brain and heart
• Hemolytic anemia

For some individuals with Wilson disease, the onset of symptoms of liver disease may be sudden and are often associated with anemia, a breakdown of red blood cells and mental confusion.

In rare cases, Wilson disease presents with brain-related or neurological symptoms such as tremors, difficulty speaking, difficulty swallowing, involuntary movements, lack of coordination, spasticity and muscle rigidity. Other rare symptoms may include kidney stones, premature arthritis and osteoporosis.

Wilson disease may be confused with other disorders that have some overlapping symptoms, including: viral hepatitis, biliary cholangitis, heavy metal poisoning, neurocanthocytosis, cerebral palsy, Sydenham chorea and Huntington disease.

Wilson disease is caused by disruptions of the ATP7B gene. The gene codes a copper transport protein that’s active in the liver to move copper from the blood to a digestive juice called bile. Bile enters the intestine through the bile ducts where it helps dissolve food, but the copper ends up the stool outside the body. More than 300 mutations of the ATP7B gene have been identified and linked to Wilson disease.

Wilson disease is inherited as an autosomal recessive trait, meaning that in order for a person to have this disorder, they must have inherited two abnormal copies – one from each parent. A person who inherits only one abnormal gene copy will be a carrier of the disorder, but not have the disorder.

Wilson disease is diagnosed after a complete patient history, thorough clinical evaluation and specialized tests that may include all or some of the following:

• Blood tests to identify low levels of ceruloplasmin, a copper carrier protein
• Urine tests to identify abnormally high levels of copper overflowing from the blood
• Slit-lamp examination of the eyes to determine if Kayser-Fleischer rings are present
• Liver biopsy and copper analysis
• Genetic studies of the patient – and potentially family members – to identify any mutations of the ATP7B gene

Wilson disease can cause irreversible neurological dysfunction and significant liver disease. For these reasons, it’s important to diagnose the disease as soon as possible and begin treatment.

Lifelong treatment for Wilson disease is necessary to lower copper in the body to nontoxic levels, prevent disease progression, and reverse any damage caused by copper accumulation in the body.

Treatment typically includes:

• A low copper diet that includes eliminating nuts, shellfish, chocolate and organ meats, and removing copper pots and bowls from cooking
• Chelation medication (such as penicillamine or trientine dihydrochloride) which draw copper out of tissues and directs it to the kidneys to be removed from the body through urination
• Medication (zinc salts) to reduce absorption of copper from foods

Patients with mild to moderate liver disease may be effectively treated with a chelation drug and may be maintained on zinc and a low copper diet.

Patients with severe liver failure may require a liver transplant.

Patients with Wilson disease will require lifelong monitoring including routine physical examinations, follow-up blood and urine tests, as well as periodic assessment of liver functions. In most cases, repeated liver biopsies are not needed.

Abruptly stopping medication for Wilson disease is dangerous as it can result in a rapid rebound of copper deposition in the body, which can be life threatening.