Wilson disease

Last revised by Lincoln J Lim on 2 Aug 2023

Wilson disease, also known as hepatolenticular degeneration, is a rare autosomal recessive disorder of copper metabolism affecting multiple systems. 

It affects 1 in 30,000-40,000 individuals 12. 1 in 90 individuals would be a heterozygous carrier 18.

The clinical presentation is non-specific and incredibly varied, typically manifesting by early adulthood 5,11,13,15:

  • hepatic manifestations: liver disease ultimately resulting in cirrhosis (tends to be seen in early-onset presentations)

  • neuropsychiatric manifestations:

    • dysarthria

    • movement disorders: dystonia, tremor, choreoathetosis, parkinsonism

    • ataxia

    • dementia

    • depression and other psychiatric symptoms

  • ocular manifestations:

  • other manifestations:

    • premature osteoarthritis

    • hemolysis and anemia

    • azure lunulae (blue nail discoloration)

    • cardiomyopathy

It is a disorder that results from abnormal ceruloplasmin metabolism, as a result of a variety of mutations in the ATP7B gene. Total body copper is elevated that has toxic effects on hepatocytes with copper deposition and resulting damage to a variety of organs, e.g. liver and brain.

Three central nervous system pathways are affected mostly:

  • serum ceruloplasmin: reduced 13,14

  • serum copper: reduced 14

  • free serum copper: increased 14

  • urinary copper: increased 14

Please see individual articles:

General treatment is focussed on chelation of the copper, and chelating agents used include zinc sulfate, trientine dihydrochloride, ammonium tetrathiomolybdate and penicillamine 7,18,22. Otherwise, specific treatment is directed towards the clinical presentation, e.g. management of complications of liver disease, management neuropsychiatric symptoms.

It was initially described by Samuel Alexander Kinnier Wilson (1878-1937), an American-born British neurologist, in 1912 as "progressive lenticular degeneration". Wilson also coined the terms extrapyramidal system and syndrome 10,20. Interestingly, Kayser-Fleischer rings were initially described a decade earlier by German physicians Bernhard Kayser (1869-1954) and Bruno Fleischer (1848-1904) in 1902 and 1903 respectively 16,17,21.

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