Wilson's disease

Question 1

What is Wilson’s disease?

Answer 1

Autosomal recessive disorder characterised by reduced biliary excretion of copper + accumulation of copper in the liver + brain, (esp. basal ganglia).

Question 2

What causes Wilson’s disease?

Answer 2

Mutation in a gene on chr 13 that codes for copper transporting ATPase (ATP7B) in hepatocytes

Question 3

What results from the mutation in Wilson’s disease?

Answer 3

Interferes with transport of copper into intracellular compartments for incorporation into caeruloplasmin
Caeruloplasmin is normally secreted into plasma or excreted in bile
Excess copper damages hepatocyte mitochondria, leading to cell death + release of free copper into the plasma
Free copper then gets deposited in tissues + impairs tissue function

Question 4

Describe the epidemiology of Wilson’s disease

Answer 4

Liver disease may present in children

Neurological disease usually presents in young adults

Question 5

What may Wilson’s disease present with?

Answer 5

Hepatitis
Liver failure
Cirrhosis

Question 6

List 4 hepatic symptoms caused by Wilson’s disease

Answer 6

Jaundice
Easy bruising
Variceal bleeding
Encephalopathy

Question 7

List 9 neurological symptoms caused by Wilson’s disease

Answer 7

Dyskinesia 
Rigidity  
Tremor  
Dystonia 
Dysarthria 
Dysphagia  
Drooling  
Dementia  
Ataxia

Question 8

List 3 psychiatric conditions caused by Wilson’s disease

Answer 8

Conduct disorder
Personality change
Psychosis

Question 9

List 4 signs of liver involvement in Wilson’s disease

Answer 9

Hepatosplenomegaly
Jaundice
Ascites/ oedema
Gynaecomastia

Question 10

Give 2 ocular signs of Wilson’s disease

Answer 10

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

Question 11

Describe LFTs in Wilson’s disease

Answer 11

High AST
High ALT
High ALP

Question 12

What other serum tests are performed in Wilson’s disease?

Answer 12

LOW serum caeruloplasmin

LOW serum copper

Question 13

Why must caution be taken when interpreting serum caeruloplasmin?

Answer 13

Caeruloplasmin is an acute phase protein so may give false-negatives if there is an underlying infectious/ inflammatory process

Question 14

What other investigations may be performed in Wilson’s disease?

Answer 14

24 hour urinary copper levels: increased
Liver biopsy: increased copper content
Genetic analysis
MRI: degeneration of basal ganglia

Question 15

Why is genetic analysis complex in Wilson’s disease?

Answer 15

Wilson’s is caused by a wide variety of gene mutations so there isn’t a simple genetic test that can be done

Question 16

What is caeruloplasmin?

Answer 16

Copper containing complex

Question 17

What mnemonic can be used to characterise Wilsons disease?

Answer 17

Copper is Hella BAD:
Ceruloplasmin decreased, Cirrhosis, Corneal deposits (KF rings), Copper accumulation, Carcinoma (hepatocellular)
Haemolytic anaemia
Basal ganglia degeneration (Parkinsonian Sx)
Asterixis
Dementia, dyskinesia, dysarthria

Question 18

Describe neurological exam findings in Wilsons disease

Answer 18

NORMAL SENSATION, MUSCLE STRENGTH + REFLEXES