Wilson's 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's 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, neurological conditions, or psychiatric disorders.
Screening and diagnostic tests: 24-hour urine copper measurement, ophthalmological 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). Pharmacological 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's 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 trans-membrane 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
- behavioural abnormalities
- presence of Kayser-Fleischer rings
- sloppy or small handwriting
Other diagnostic factors
- cognitive impairment
- personality change
- abnormal extra-ocular movements
- normal sensation, muscular strength, and reflexes
- history of gastrointestinal bleeding
- liver tenderness
- spider angiomata
- peripheral oedema
- ATP7B gene mutation
- family history of Wilson's disease
1st investigations to order
- 24-hour urinary copper
- slit-lamp examination
- 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 (neurological disease or hepatic disease without liver failure)
- Hepatitis B
- Hepatitis C
- Investigation and management of Wilson’s disease
- Investigation and management of Wilson's disease
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