Overview
Wilson’s disease (WD) is an autosomal recessive disorder characterised by impaired Wilson disease protein (ATP7B protein) function. This protein normally moves excess copper into bile where it is incorporated into caeruloplasmin for excretion. If copper is not bound to caeruloplasmin using the WD protein, it quickly degrades.
Epidemiology
- Wilson’s disease has a prevalence of around 3 per 100,000
- Patients tend to present aged 10-40 years, however, symptoms can occur in any age
Presentation
WD should be suspected in patients that have neurological symptoms and evidence of liver disease. Features may include:
- Features of hepatitis or cirrhosis
- Parkinsonism – tremors, rigidity, bradykinesia, postural instability:
- This is because, in the brain, most copper is deposited in the basal ganglia
- Incoordination
- Cognitive impairment and dementia
- Psychiatric problems – depression, personality changes
- Kayser-Fleisher rings:
- Brown rings in the periphery of the iris due to copper deposition
Investigations
- LFTs:
- AST and ALT are elevated
- Slit-lamp examination:
- Assesses Kayser-Fleisher rings
- Serum caeruloplasmin:
- Reduced
- May be normal in inflammation as it is an acute-phase reactant
- Serum copper:
- Reduced
- This may seem unusual given that WD is a disease of copper excess. As mentioned above, the WD protein is non-functional, so copper is not incorporated in caeruloplasmin, therefore caeruloplasmin degrades quickly. Caeruloplasmin is needed to carry copper in the serum, but since it is low, serum copper is also low. The copper is instead deposited in tissues.
Management
Overview
- 1st-line: penicillamine
- This is a copper-chelating agent
- Liver transplantation may be necessary
Complications
- Liver failure and cirrhosis
Prognosis
- If left untreated, WD is progressive and can be fatal
- Early diagnosis and treatment may reverse some neurological signs
- Cirrhosis cannot be reversed
