WILSON’S DISEASE

Question 1

What two things does the liver normally do to copper?

which protein is required for these actions?

Answer 1

• Excretes copper into bile
• Incorporates copper into ceruloplasmin (transport molecule) → released into serum where it carries copper to other organs

► Both functions require hepatic copper transport protein ATP7B

Question 2

What is the dominance of Wilson’s disease?

What is the mutation?

What does this cause?

Answer 2

• Autosomal recessive
• Mutation of ATP7B gene (chromosome 13)

⇒ copper not excreted into bile + ceruloplasmin not secreted into plasma

• Disease causes accumulation of copper in liver → damage. Also deposits in brain, cornea, kidneys, joints

Question 3

What are 3 diagnostic hallmarks of Wilson’s disease?

Answer 3

1. Low ceruloplasmin level → LOW total serum copper level despite copper overload

Note: there is still increased free serum copper, which is what causes deposition in organs

2. Kayser-Fleischer rings → corneal copper deposits, not seen in any other condition so very good diagnostic test (slit lamp)
3. High urinary copper excretion → 24 hour test

Question 4

Mean age of onset of Wilsons disease

Answer 4

12-23 yrs

Question 5

What does Wilsons disease cause in the liver?

Answer 5

• Cirrhosis
• Hepatocellular carcinoma: needs screening

Question 6

Why would somebody with Wilsons disease develop parkinsonism?

Answer 6

Basal ganglia deposition of copper

Question 7

Explain why somebody with Wilsons disease might develop a coombs negative haemolytic anaemia

Answer 7

• Deposition of copper in RBCs causes haemolysis
• Coombs’ test is used to detect antibodies that act against surface of RBCs. Presence indicates haemolytic anemia