Wilson's disease

Question 1

Define Wilson’s disease.

Answer 1

AUTOSOMAL recessive

Disorder in which there is reduced biliary excretion of copper and accumulation of it in the liver and brain, especially in basal ganglia

AKA hepatolenticular degeneration

Question 2

Which gene is affected in Wilson’s disease?

Answer 2

ATP7B gene mutation found on chromosome 13

Codes for copper transporting ATPase in hepatocytes

Question 3

Describe the pathophysiology of Wilson’s disease.

Answer 3

High copper –> toxicity by oxidant damage and damages mitochondria, causing cell death and release of free copper into plasma which is subsequently deposited in other tissues.

Mutations interfere with transport of copper into intracellular compartments for incorporation into caeruloplasmin (and secretion into plasma) or excretion into bile.

Question 4

What are the risk factors for Wilson’s disease?

Answer 4

ATP7B gene mutation

(WEAK: Non-vegetarian diet = less copper is bioavailable from vegetables than from meat)

Question 5

What is the typical presentation of Wilson’s disease?

Answer 5

Usually aged 10-25yrs at presentation

Liver - hepatitis, cirrhosis, liver failure, jaundice, easy bruising, variceal bleeding, encephalopathy

Neurological - dyskinesia, rigidity, tremor, dystonia, dysarthria, dysphagia, drooling, dementia, ataxia

Psychiatric - conduct disorder, personality change, psychosis.

Question 6

What are the signs of Wilson’s disease on examination?

Answer 6

• Liver - hepatosplenomegaly, jaundice, ascites/oedema, gynaecomastia.
• Neurological - dyskinesia, rigidity, tremor, dystonia, dysarthria, dysphagia, drooling, dementia, ataxia.
• Eyes - Green or brown Kayser-Fleischer ring at the corneal limbus, sunflower cataract (copper accumulation in th lens, seen with slit lamp).

Question 7

What investigations would you do for Wilson’s disease?

Answer 7

Bloods:

• LFTs - abnormal, especially high AST, ALT, AlkPhos
• Blood ceruloplasmin - LOW (but can give false negatives as it is an acute phase protein) - <180mg/L
• Serum total copper - LOW (95% of plasma copper is carried by ceruloplasmin)
• Serum free copper - HIGH
• Genetic analysis - test for ATP7B, and DNA haplotype testing for siblings of carrier

Other:

• Slit lamp test for Kayser-Fleischer rings
• Liver biopsy - increased Cu content

Question 8

How do you manage Wilson’s?

Answer 8

• Specialist unit medical treatment - usually involves copper chelators e.g. D-penicillamine
• Genetic counselling
• Liver transplant if necessary

Question 9

What is the epidemiology of Wilson’s disease?

Answer 9

• Affects 1/30,000
• Carrier frequency 1/100
• Liver disease may present in children (>5 years)
• Neurological disease presents in young adults

Treatment improves outcomes if patient presents early enough

Question 10

Which part of the brain is most affected in Wilson’s?

Answer 10

Basal ganglia degeneration especially in the putamen and globus pallidus

Question 11

What is shown and what is the cause of this?

Answer 11

Kayser-Fleischer ring - deposition of copper in Descemet membrane of the iris periphery.