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, ophthalmological 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). Neurological presentations are treated with zinc.
Maintenance and pre-symptomatic therapy: zinc. If zinc-intolerant, trientine next best choice for maintenance.
Wilson's 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 neurological disease. Siblings of a patient have a 25% chance of being affected, and family work-up 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 behavioural 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 oedema
- hepatojugular reflux
- ATP7B gene mutation
- non-vegetarian diet
1st investigations to order
- Liver function tests
Investigations to consider
- 24-hour urine copper
- full blood count
- slit-lamp examination
- blood ceruloplasmin
- liver biopsy for hepatic presentation
- liver biopsy for neurological/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/pre-symptomatic or liver disease (no hepatic failure) or following completion of therapy for liver disease
- Viral hepatitis B
- Viral hepatitis C
- Diagnosis and treatment of Wilson disease: an update
Hepatitis C: what is it?
Hepatitis C: what treatments work?More Patient leaflets
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