Wilson's Disease

Question 1

Define Wilson’s Disease

Answer 1

• DEFINITION: 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.

So it is a defect in the metabolism of copper

Also known as hepatolenticular degeneration.

Question 2

Explain the aetiology/risk factors for Wilson’s disease

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

Recognise the presenting symptoms of Wilson’s disease

Answer 3

• Liver
○ May present with: hepatitis, liver failure, cirrhosis
○ Symptoms:
• Jaundice
• Easy bruising
• Encephalopathy - brain disease/damage
• Variceal bleeding -Varices are dilated blood vessels in the esophagus or stomach caused by portal hypertension.

• Neurological
○ Dyskinesia - impaired voluntary movement
○ Rigidity
○ Tremor
○ Dystonia
○ Dysarthria
○ Dysphagia
○ Drooling
○ Dementia
○ Ataxia

• Psychiatric
○ Conduct disorder
○ Personality change
○ Psychosis

Question 4

Recognise the signs of Wilson’s disease on physical examination

Answer 4

• Liver
○ Hepatosplenomegaly
○ Jaundice
○ Ascites/oedema
○ Gynaecomastia

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

Question 5

Identify appropriate investigations for Wilson’s disease

Answer 5

• Bloods
○ Serum copper
○ 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

• 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