Wilson's disease

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LogoKeyPointsBox.pngConsider whenever[1]:
  • Liver abnormalities of uncertain cause
  • New onset movement disorders

Wilson's disease[2] (Progressive hepatolenticular degeneration, Wilson disease) is an autosomal recessive condition with copper accumulation due to impairment of biliary excretion.

Contents

Aetiology

  • Mutations of the ATP7B gene that codes for a copper transporting P-type ATPase. It has dual synthetic and excretory roles.

Clinical Presentation

  • Many by familial clinical screening after index case
  • Index cases usually present in late teens but can be in their 50's and rarely in younger children. Neurological presentation tends to be older (by 5 years) than hepatic presentation[3]
  • Hepatic disease (about 2/3rds presenting first clinically)
    • Cirrhosis
    • Elevated aminotransferases
    • Chronic hepatitis
    • Fulminant hepatic failure (+/− Coombs negative haemolytic anaemia), about 5% of presentations
  • Movement disorders (in about 40% presenting first clinically)
  • Psychiatric symptoms
    • Depression
    • Neuroses
    • Personality changes
    • Psychosis

It can also cause:

Diagnosis

Can be tricky given multisystem disorder and limited sensitivity/specificity of tests. Heterozygotes may also have borderline results.

  • In classic presentation in young adult life two of the following are diagnostic
  • May require extensive tests of copper metabolism especially with severe hepatic presentation, where up to 50% can have normal caeruloplasmin (an acute phase reactant) eg
    • Non-caeruloplasmin-bound serum copper
    • 24-h urinary copper excretion - can be abnormal in other chronic liver diseases, however. Excretion of >25micromol/24hr after penicillamine is a diagnostic test in children
    • Liver copper content (>250mcg/g dry weight) - best test when others ambiguous
  • In fulminant hepatic failure the following features may suggest diagnosis:[4]
    • Haemolysis (Coombs negative)
    • Increased urinary copper (range 844-9375 microg/24 h)
    • High non-caeruloplasmin copper (range 325-1743 microg/l)
    • Alkaline phosphatase to Bilirubin ratio of less than 1 has 86% sensitivity and 50% specificity in children [5]
  • Genetic screening of limited utility due to number of known mutations (more than 300)
  • Opalski cells (?degenerating astrocytes) on brain biopsy are distinctive for Wilson's disease[6]
    • Fairly large (up to 35 μm in diameter), with fine granular cytoplasm and slightly abnormal nuclei

Treatment

  • Diet - chocolate, liver, nuts, mushrooms, and shellfish are high in copper
  • Zinc - reduces copper absorption from gut. Monotherapy is an option for maintenance therapy.
  • Chelation
    • D-penicillamine - but note side effects, and some patients with neurological disease deteriorate on starting treatment
    • Trientine - perhaps less side effects
  • Liver transplantation - curative, except for long-standing neurological disease. Indicated for fulminant hepatic failure.

Monitoring

  • Neurological function
  • Liver function tests
  • 24hr urinary copper excretion (aim for less than 2 micromol/d)
  • Non-caeruloplasmin bound copper of 50-150mcg/L

References

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