Wilson disease, also known as hepatolenticular degeneration, is a rare autosomal recessive disorder of copper metabolism affecting multiple systems.
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Epidemiology
It affects 1 in 30,000-40,000 individuals 12. 1 in 90 individuals would be a heterozygous carrier 18.
Clinical presentation
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)
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neuropsychiatric manifestations:
dysarthria
movement disorders: dystonia, tremor, choreoathetosis, parkinsonism
ataxia
dementia
depression and other psychiatric symptoms
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ocular manifestations:
Kayser-Fleischer rings in the cornea 11
sunflower cataracts 22
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other manifestations:
premature osteoarthritis
haemolysis and anaemia
azure lunulae (blue nail discoloration)
cardiomyopathy
Pathology
It is a disorder that results from abnormal caeruloplasmin 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:
dentatorubrothalamic tract
pontocerebellar tract
Markers
serum caeruloplasmin: reduced 13,14
serum copper: reduced 14
free serum copper: increased 14
urinary copper: increased 14
Radiographic features
Please see individual articles:
Treatment and prognosis
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.
History and etymology
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.