Wilson Disease

Question 1

define Wilson Disease?

Answer 1

Wilson’s disease is an autosomal-recessive disease of copper accumulation and copper toxicity caused by mutations in the ATP7B gene on chromosome 13 , which is part of the biliary excretion of copper pathway

=> accumulation of copper in liver and brain-> especially in basal ganglia=> HEPATOTENTICULAR DEGENERATION

Question 2

summarise the epidemiology of Wilson’s disease?

Answer 2

Liver disease may be present in young children

Neurological disease usually presents in young adults

Question 3

outline the aetiology of Wilson’s Disease/

Answer 3

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

copper absorption and transport into liver intact-> interferes with transport of copper into intracellular compartments for incorporation into caeruloplasmin ( copper containing complex)

caeuroplasmin in normally secreted into plasma or excreted in bile

excess copper damages hepatocyte mitochondria-> cell death=> release of free copper into the plasma

free copper gets deposited in tissues-> impairs tissue function

Question 4

what are the risk factors for Wilsons disease?

Answer 4

ATP7B gene mutation

non-vegetarian diet

Question 5

what are the threee classes sof symptoms for wilsons Disease?

Answer 5

Liver

Neurological

Psychiatric

Question 6

what are the liver symptoms for Wilson’s disease?

Answer 6

hepatitis, liver failure, cirrhosis

jaundice 
liver tenderness
easy bruising 
variceal bleeding 
encephalopathy

Question 7

what are the neurological symptoms for Wilsons Disease?

Answer 7

dyskinesia 
rigidity 
tremor 
dystonia ( in upper extremities) 
dysarthria 
dysphagia 
drooling 
dementia
ataxia 
abnormal extra- ocular eye movements ( abnorma saccade, diplopia)

Question 8

what are the psychiatric symptoms of Wilson’s disease?

Answer 8

conduct disorder
personality change
psychosis

Question 9

what are the signs of Wilson’s disease on physical examination?

Answer 9

liver

• hepatomegaly
• ascites/oedema
• jaundice
• gynaecomastia

eyes

• Kayser- Fleischer Rings-> visible to naked eye in late stages, early stages seen with slit lamp
• sunflower cataract ( copper accumulation in lens-> seen with slit lamp)

blue nails

Question 10

summarise Wilson’s disease?

Answer 10

Parkinsonism, and neuropsych symptoms ( personality change, dysarthria, dyskinesia) and jaundice

Question 11

what are the appropriate investigations for Wilson’s disease?

Answer 11

bloods

24 hour urinary copper- increased

liver biospy- increased copper content (>250mg/g)

genetic analysis- Causative mutations found on both copies of the gene definitively diagnose Wilson’s disease. A causative mutation found on one gene indicates a heterozygous carrier.

MRI- degeneration in basal ganglia, fronto-temporal, cerebellar and brainstem

Question 12

describe bloods in Wilson’s disease?

Answer 12

LFTs: high AST, high ALP, ALT, bilirubin and low albumin

FBC- portal HT-> cause low plt and cause low WBC

Low serum caeruloplasmin (<180mg/dL)

Question 13

why is caeruloplasmin not the best investigation?

Answer 13

caeruloplasmin is an acute phase protein so may give false-negatives if there is an underlying infectious/inflammatory process or pregnancy
Can also give false-positives in protein deficient state or any other chronic liver disease can decrease synthesis

Question 14

what may be seen on a MRI in Wilson’s disease?

Answer 14

degeneration in basal ganglia, fronto-temporal, cerebellar and brainstem

Question 15

summarise Wilson’s disease?

Answer 15

Copper is Hella Bad

Ceruloplasmin decreased, Cirrhosis, Corneal deposits (Kayser-Fleischer rings),
Copper accumulation, Carcinoma (hepatocellular)
Hemolytic anemia
Basal ganglia degeneration (parkinsonian symptoms)
Asterixis
Dementia, Dyskinesia, Dysarthria

Question 16

what is the current treatment for Wilson’s disease?

Answer 16

use zinc to block intestinal copper resorption and trientine to increase urinary copper excretion