Wilson's disease is an autosomal-recessive disease of copper accumulation and toxicity caused by a defect in an enzyme involved in the biliary excretion of excess copper.
Affects up to 1 in 40,000 people.
Diagnosis often missed; should be considered in patients aged 10 to 40 years with hepatitis, cirrhosis, hepatic decompensation, and symptoms suggestive of movement or psychiatric disorders.
Screening and diagnostic tests: 24-hour urine copper measurement, ophthalmologic slit-lamp examination for Kayser-Fleischer (KF) rings, blood ceruloplasmin levels, and liver biopsy with measurement of quantitative copper.
Unlike many genetic disorders, it is treatable. Hepatic presentations are treated with a combination of trientine and zinc (liver transplantation if liver failure severe). Neurologic presentations are treated with zinc.
Maintenance and presymptomatic therapy: zinc. If zinc-intolerant, trientine next best choice for maintenance.
Wilson disease is an autosomal-recessive disease of copper accumulation and copper toxicity caused by mutations in the ATP7B gene, which is part of the biliary excretion of copper pathway. Patients are usually aged 10 to 40 years and present with either hepatic disease or a movement disorder neurologic disease. Siblings of a patient have a 25% chance of being affected, and family workup allows the diagnosis to be made in those who do not yet have symptoms.
History and exam
Key diagnostic factors
- history of hepatitis
- history of behavioral abnormalities
- sloppy or small handwriting
Other diagnostic factors
- abnormal extraocular movements
- normal sensation, muscular strength, and reflexes
- history of gastrointestinal bleeding
- liver tenderness
- spider angiomata
- peripheral edema
- hepatojugular reflux
- ATP7B gene mutation
- nonvegetarian diet
1st investigations to order
- Liver function tests
Investigations to consider
- 24-hour urine copper
- complete blood count
- slit-lamp exam
- blood ceruloplasmin
- liver biopsy for hepatic presentation
- liver biopsy for neurologic/psychiatric presentation
- MRI brain
- blood free copper
- DNA testing for ATP7B mutations
- DNA haplotype testing (siblings of an affected patient)
hepatic failure, severe (Nazer score ≥10)
hepatic failure, mild to moderate (Nazer score 1 to 9)
asymptomatic/presymptomatic or liver disease (no hepatic failure) or following completion of therapy for liver disease
George J. Brewer, MD
Morton S. and Henrietta K. Sellner Emeritus Professor of Human Genetics
Department of Human Genetics
University of Michigan Medical School
GJB 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.
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