Wilson's Disease Flashcards
Define Wilson’s Disease
• 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.
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 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
Recognise the presenting symptoms of Wilson’s disease
• 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
Recognise the signs of Wilson’s disease on physical examination
• Liver ○ Hepatosplenomegaly ○ Jaundice ○ Ascites/oedema ○ Gynaecomastia
• Eyes
○ Kayser-Fleischer Rings
○ Sunflower cataract (copper accumulation in the lens, seen with a slit lamp)
Identify appropriate investigations for Wilson’s disease
• 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