Wilson disease is an autosomal-recessive disease of copper accumulation and toxicity caused by a defect in an enzyme involved in the excretion of excess copper.
Estimated prevalence is 1 in 30,000 to 1 in 50,000, with no sex or ethnic predominance.
Wilson disease is a systemic disease that can often mimic other conditions, commonly leading to delayed diagnosis or misdiagnosis. It should be considered in patients with abnormal liver enzymes, cirrhosis, neurologic conditions, or psychiatric disorders.
Screening and diagnostic tests: 24-hour urine copper measurement, ophthalmologic slit-lamp examination for Kayser-Fleischer (KF) rings, blood ceruloplasmin levels, serum copper, and liver biopsy with measurement of quantitative copper. If available, genetic testing for ATP7B can be done.
Treatment regimens vary depending on the clinical presentation and treatment phase (initial or maintenance). Pharmacologic therapy includes the oral chelators penicillamine (as the D-isomer) and trientine, which increase urinary copper excretion, and zinc salts, which decrease alimentary copper absorption. In certain severe hepatic cases, liver transplantation can be curative.
Wilson disease is an autosomal-recessive disease of copper overload caused by mutations in the ATP7B gene. ATP7B encodes a metal P-type ATPase that facilitates transmembrane transport of copper within hepatocytes. Lack of the protein leads to decreased copper excretion from the liver and copper overload in hepatocytes. When hepatic storage capacity is exceeded, copper is released into the circulation and deposited in other organs.
History and exam
Key diagnostic factors
- elevated serum aminotransferases
- history of hepatitis
- acute liver failure
- behavioral abnormalities
- presence of Kayser-Fleischer rings
- sloppy or small handwriting
Other diagnostic factors
- cognitive impairment
- personality change
- abnormal extraocular movements
- normal sensation, muscular strength, and reflexes
- history of gastrointestinal bleeding
- liver tenderness
- spider angiomata
- peripheral edema
- ATP7B gene mutation
- family history of Wilson disease
1st investigations to order
- 24-hour urinary copper
- slit-lamp exam
- serum ceruloplasmin
Investigations to consider
- liver biopsy
- MRI brain
- non-ceruloplasmin-bound copper concentration (NCC)
- DNA testing for ATP7B mutations
- direct measurement of ATP7B peptide
hepatic failure, severe (Nazer score ≥10 or Kings Wilson Index score ≥11)
hepatic failure, mild to moderate (Nazer score ≤9 or Kings Wilson Index score ≤10)
symptomatic (neurologic disease or hepatic disease without liver failure)
Michael L. Schilsky, MD, FAASLD
Professor of Medicine and Surgery
Divisions of Digestive Diseases and Transplant and Immunology
Yale School of Medicine
MS is an author of multiple references in this topic.
Uyen Kim To, MD
Assistant Professor of Medicine
Division of Digestive Diseases
Yale School of Medicine
UKT declares that she has no competing interests.
Professor Michael Schilsky and Dr Uyen Kim To would like to gratefully acknowledge Professor George Brewer, a previous contributor to this topic.
GB is an author of several references cited in this topic.
Valentina Medici, MD
Division of Gastroenterology and Hepatology
Department of Internal Medicine
University of California Davis Medical Center
VM declares that she has no competing interests.
Giacomo C. Sturniolo, MD
Professor of Gastroenterology
Department of Surgical and Gastroenterological Sciences
University of Padua
GCS declares that he has no competing interests.
- Hepatitis B
- Hepatitis C
- Investigation and management of Wilson's disease
- Wilson's disease in children
Hepatitis C: what is it?
Hepatitis C: what treatments work?More Patient leaflets
- Log in or subscribe to access all of BMJ Best Practice
Use of this content is subject to our disclaimer