Wilson’s Disease


  • Rare autosomal recessive disorder of copper metabolism (worldwide prevalence of 1:30,000
    • Most caused by mutations of the ATP7B gene (ch13)
      • Encodes a protein involved in copper-transport (P-type ATP family)- primarily exporting copper out of cells
  • Normally, dietary copper is absorbed from the stomach/duodenum and rapidly taken up by the liver where it is stored and added into caeruloplasmin, before being secreted into the blood.  Excess copper is usually excreted in bile.
    • In Wilson’s disease, most patients fail to synthesise caeruloplasmin, although this is not always the case.


  • Usually presents between 5-45 years old
  • Hepatic disease occurs early (childhood/adolescence)
    • Episodes of acute hepatitis which can progress to fulminant liver failure (copper is then released into the bloodstream causing haemolysis and renal tubular necrosis)
    • Alternatively, chronic hepatitis can develop insidiously and may present with cirrhosis/portal hypertension etc.
    • I.e. any patient <40 with acute/chronic hepatitis with no underlying cause should be investigated for Wilson’s
  • Neurological damage causes basal ganglion syndromes and dementia (late adolescence)
    • Extrapyramidal symptoms e.g. tremor, chorea, dystonia, parkinsonism, dementia
    • First presentation may be of ‘clumsiness’
    • Can be prevented if treatment started before onset (i.e. identified early by liver investigation)
  • Other features include renal tubular damage and osteoporosis (rarely presenting features)
  • On Examination, the pathognomonic feature is Kayser-Fleischer rings
    • Seen in 60% of adults with Wilson’s (less common in children)
    • Greenish-brown discolourations of the corneal margin (often first in the superotemporal region)
    • Disappear with treatment



  • Serum caeruloplasmin (usually low but this is not specific for Wilson’s)
  • Measure copper levels
    • Free serum copper
    • Urine copper excretions (often whilst given D-penicillamine- see management below)
    • Hepatic copper content (biopsy)


  • Penicillamine is a copper-binding agent which causes cupriuresis (urinary excretion of copper)
    • Initial dose is usually higher (e.g. 2g/day) until disease is in remission, then can be reduced but must be taken for life
    • Can be toxic in up to a third, causing rashes, protein-losing nephropathy, lupus-like syndrome and bone marrow depression
      • Zinc or trientine dihydrochloride are alternatives
  • Liver transplant can be considered for patients with fulminant liver failure
  • First degree relatives should be investigated and also treated, even if asymptomatic, to avoid complications

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

%d bloggers like this: