Wilson's Disease

Question 1

Define

Answer 1

an autosomal recessive disorder characterised by reduced biliary excretion of copper and accumulation of copper in the liver and brain, especially in the basal ganglia. Also known as hepatolenticular degeneration.

Question 2

Causes

Answer 2

• Mutation in a gene on chromosome 13 that codes for copper transporting ATPase (ATP7B) in hepatocytes
• This interferes with the transport of copper into the intracellular compartments for incorporation into caeruloplasmin (copper containing complex)
• Caeruloplasmin is normally secreted into plasma or excreted in bile
• Excess copper damages the hepatocyte mitochondria, leading to cell death and release of free copper into the plasma
• This free copper then gets deposited in tissues and impairs tissue function

Question 3

Epidemiology

Answer 3

Liver disease may present in children

Neurological disease usually presents in young adults

Question 4

Symptoms

Answer 4

Liver

• May present with: hepatitis, liver failure, cirrhosis
• Symptoms:
  
  • Jaundice
  • Easy bruising
  • Variceal bleeding
  • Encephalopathy

Neurological

• Dyskinesia
• Rigidity
• Tremor
• Dystonia
• Dysarthria
• Dysphagia
• Drooling
• Dementia
• Ataxia

Psychiatric

• Conduct disorder
• Personality change
• Psychosis

Question 5

Sings

Answer 5

Liver

• Hepatosplenomegaly
• Jaundice
• Ascites/oedema
• Gynaecomastia

Eyes

• Kayser-Fleischer Rings
• Sunflower cataract (copper accumulation in the lens, seen with a slit lamp)

Question 6

Investigations

Answer 6

Bloods

• LFTs: high AST, ALT, ALP
• Low serum caeruloplasmin
  
  • NOTE: caeruloplasmin is an acute phase protein so may give false-negatives if there is an underlying infectious/inflammatory process
• Serum copper

24 hour urinary copper levels - increased in Wilson’s disease

Liver biopsy - increased copper content

Genetic analysis - Wilson’s is caused by a wide variety of gene mutations so there isn’t a simple genetic test that can be done