A genetic disorder which results from a defective ATP7B gene causes impaired copper metabolisim and excess deposition of copper in tissues

Liver + neurological + psychiatric Sx = Wilson’s

Pathophysiology:

Wilson's disease is an autosomal recessive disorder characterised by excessive copper deposition in the tissues.

Metabolic abnormalities include increased copper absorption from the small intestine and decreased hepatic copper excretion. Wilson's disease is caused by a defect in the ATP7B gene located on chromosome 13. This encodes an ATPase responsible for:

• excreting copper in bile
• forming caeruloplasmin (main copper carrying molecule in the blood)

Therefore plasma copper is paradoxically low as it is rapidly deposited in the CNS and the liver

The onset of symptoms is usually between 10 - 25 years. Children usually present with liver disease whereas the first sign of disease in young adults is often neurological disease

Clinical features

Features result from excessive copper deposition in the tissues, especially the brain, liver and cornea:

• liver: hepatitis, cirrhosis
• neurological:
  • basal ganglia degeneration: in the brain, most copper is deposited in the basal ganglia, particularly in the putamen and globus pallidus
  • Akinesia, tremor, ataxia, dystonia (leads to contractures)
  • also: asterixis, chorea, dementia, parkinsonism
  • speach problems: dysarthria
• Psychiatric:
  • May be present before hepatic/neuro signs in 1/3 of patients
  • personality changes, sexual exhibitionism, impulsiveness, labile mood, inappropriate behaviour, depression, paranoia, schizophrenia, suicide
• Kayser-Fleischer rings
  • green-brown rings in the periphery of the iris
  • due to copper accumulation in Descemet membrane
  • present in around 50% of patients with isolated hepatic Wilson's disease and 90% who have neurological involvement
• blue nails