Wilson Disease Research Paper

Wilson disease

What is Wilson disease?

Wilson disease is a medical condition characterized by liver, neurologic, and psychological abnormalities related to the deposition of copper in the liver and brain. The condition occurs due to impaired copper metabolism, which result in copper build up in tissues. Most patients are diagnosed at age 5-35. Untreated Wilson disease frequently results in liver injury that often advances to liver cirrhosis and end-stage liver disease. Copper accumulation in the brain leads to movement abnormalities that progressively worsen – in late stages patients often have absent movement and speech (akinetic mutism).

If left untreated, Wilson disease leads to death – most patients die from liver failure. Due to

the importance of this condition, it is critical that patients understand its causes, symptoms, and treatment. By the end of this article, you will have the answers to these essential questions
• What causes Wilson disease?
• How common is Wilson disease?
• What are the symptoms and signs of Wilson disease?
• How is Wilson disease diagnosed?

• How is Wilson disease treated?

What causes Wilson disease?

Wilson disease is caused by impaired copper metabolism that leads to the accumulation of copper in the body. Copper deposits into organs such as the liver and brain, producing abnormal symptoms and signs.

Elevated copper levels in the liver lead to injury and inflammation. Long-term liver inflammation typically causes scarring of the liver (cirrhosis). Patients may develop signs of chronic liver disease or liver failure. Copper deposition in brain tissue also results in neuronal injury and death, resulting in slurred speech, movement abnormalities, and depression. This may progressively worsen into a condition called akinetic mutism - absent movement or speech.

How common is Wilson disease?

Wilson disease is uncommon in the United States. Studies show that the condition affects men and women equally. Women have a higher likelihood of developing acute liver failure. Wilson disease has a worldwide prevalence of approximately 1 case per 30,000 live births. About 1 person in 90 has an abnormal copy of the ATP7B gene, which is highly associated with the disease.

What are the symptoms and signs of Wilson

disease?
Symptoms of Wilson disease often include a combination of liver, neurologic, and psychological features:
Hepatic findings in Wilson disease may include acute hepatitis, chronic hepatitis, steatosis (fatty liver), and cirrhosis (scarring of the liver). Liver cirrhosis may produce the following complications:
• Confusion – hepatic encephalopathy
• Easy bleeding & bruising – coagulopathy
• Jaundice – yellow discoloration of skin
• Swelling in the legs – lower extremity edema
• Ascites – increased intra-abdominal fluid
• Spontaneous bacterial peritonitis (SBP)
• Bad breath – fetor hepaticus
• Increased risk for infection
• Gynecomastia and loss of pubic hair
• Upper gastrointestinal bleeding – esophageal varices
• Liver cancer
The neurologic manifestations of Wilson disease often include:
• Dysarthria – slurred speech
• Gait abnormalities – trouble walking, ataxia
• Dystonia – abnormal muscle contraction/tone
• Tremor – shaking
Psychological symptoms often occur with neurologic disease and include:
• Depression
• Personality change
• Irritability
Kayser-Fleischer rings are a highly specific finding on physical examination characterized by brown discoloration around the iris. It is caused by copper deposition in Descemet’s membrane in the cornea of the eye.
How is Wilson disease diagnosed?
The diagnosis of Wilson disease is suggested based on symptoms, history, and physical examination, but typically confirmed with laboratory and imaging studies. Your doctor will typically begin by ordering a CMP (comprehensive metabolic panel). If you have abnormal liver function they will usually order serum ceruloplasmin and copper levels. Additional blood tests often include a CBC (complete blood cell count) and coagulation studies (PT/INR, PTT). They will also usually check your cholesterol levels and screen for diabetes – these are risk factors for fatty liver disease.
Patients with elevated serum copper or low ceruloplasmin levels typically require a 24-hour urinary copper excretion. Individuals with suspected Wilson disease may be referred to an ophthalmologist for an ocular slit-lamp examination evaluating for Kayser-Fleischer rings.
Individuals with signs of chronic liver disease generally require abdominal ultrasound or CT scan. Occasionally, your doctor with order an MRI of the abdomen. Patients with advanced liver disease may require upper endoscopies to screen for esophageal varices.
How is Wilson disease treated?
Wilson disease is treated with lifelong medications that remove copper from tissues and prevent its reaccumulation. Patients are often prescribed chelating agents such as D- Cuprimine (penicillamine) or Syprine (trientine). Patients that are intolerant of chelating agents may benefit from zinc therapy.
Your doctor will typically monitor you regularly by checking a 24-hour urine copper levels and free serum copper levels. Individuals with Wilson disease and acute liver failure often require liver transplantation.
Summary:
• Wilson disease is a medical condition characterized by liver, neurologic, and psychological abnormalities related to the deposition of copper in the liver and brain.
• It is caused by impaired copper metabolism. Most patients are diagnosed at age 5-35.
• Hepatic findings in Wilson disease may include acute hepatitis, chronic hepatitis, liver cirrhosis, and steatosis (fatty liver).
• Complications of liver cirrhosis include hepatic encephalopathy, coagulopathy, jaundice, lower extremity edema, ascites, spontaneous bacterial peritonitis, and upper gastrointestinal bleeding.

One of the most fearful complications is liver cancer.

• The neurologic manifestations of Wilson disease often include slurred speech, trouble walking, ataxia, dystonia, and tremor (shaking).

• Psychological features often occur with neurologic disease. These symptoms typically include mood disorder (eg, depression, anxiety), personality change, and irritability.

• Kayser-Fleischer rings are a highly specific finding on physical examination characterized by brown discoloration around the iris. They are caused by copper deposition in Descemet’s membrane in the cornea of the eye.

• The diagnosis of Wilson disease is based on history, symptoms, and physical examination findings, but requires laboratory tests for confirmation.

• Your doctor will begin by ordering a comprehensive metabolic panel. If you have abnormal liver function they will typically order serum ceruloplasmin and copper levels.

• Wilson disease is treated with chelating agents eliminate copper from the body. This typically include D- Cuprimine (penicillamine) or Syprine

(trientine).
• Patients that are intolerant of chelating agents may benefit from zinc therapy.
• Your doctor will typically monitor you regularly by checking a 24-hour urine copper levels and free serum copper levels to ensure that treatment is effective.
• Individuals with Wilson disease and acute liver failure often require liver transplantation.
References:
1. Taly AB, Meenakshi-Sundaram S, Sinha S, et al. Wilson disease: description of 282 patients evaluated over 3 decades. Medicine (Baltimore) 2007; 86:112.
2. Roberts EA, Schilsky ML, Division of Gastroenterology and Nutrition, Hospital for Sick Children, Toronto, Ontario, Canada. A practice guideline on Wilson disease. Hepatology 2003; 37:1475.
3. Roberts EA, Schilsky ML, American Association for Study of Liver Diseases (AASLD). Diagnosis and treatment of Wilson disease: an update. Hepatology 2008; 47:2089.