Wilson's Disease

Question 1

Definition

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

Aetiology

Answer 2

Explain the aetiology/risk factors for Wilson’s disease
• 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
forincorporation 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

Presenting symptoms (liver)

Answer 4

o May present with: hepatitis, liver failure, cirrhosis

o Symptoms:
• Jaundice
• Easy bruising
• Variceal bleeding
• Encephalopathy

Question 5

Presenting symptoms (neurological)

Answer 5

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

Question 6

Presenting symptoms (psychiatric)

Answer 6

o Conduct disorder
o Personality change
o Psychosis

Question 7

Signs on physical examination

Answer 7

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

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

Question 8

Investigations (bloods)

Answer 8

o LFTs: high AST, ALT, ALP

o Low serum caeruloplasmin
• NOTE: caeruloplasmin is an acute phase protein so may give false-negatives if there is an underlying infectious/inflammatory process

o Serum copper

Question 9

Investigations (other)

Answer 9

• 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