Wilson's disease

Question 1

What is Wilson’s disease?

Answer 1

Autosomal recessive disease of copper accumulation and toxicity.

Question 2

What is an alternative name for Wilson’s disease?

Answer 2

Hepatolenticular degeneration.

Question 3

What is the aetiology of Wilson’s disease?

Answer 3

Autosomal recessive caused by mutations in the ATP7B gene. Defect in an enzyme involved in biliary excretion of excess copper – copper-transporting ATPase in hepatocytes. Mutations interfere with transport of copper intracellularly for incorporation into ceruloplasmin and secretion into the plasma.

Question 4

What is the pathophysiology of Wilson’s disease? Two main areas?

Answer 4

Copper accumulation in the liver and subsequent hepatocyte death leads to release of copper into plasma where it deposits into tissues and causes toxicity by oxidant damage. The damage occurs in mitochondria, peroxisomes, microtubules, DNA and plasma membranes leading to cell injury, inflammation and cell death. In Wilson’s copper is initially stored in the liver where this inflammation and cell injury leads to hepatitis and eventually hepatic failure. The basal ganglia is sensitive to copper accumulation (coordinates movement).

Question 5

What are the classifications of Wilson’s disease? (x4)

Answer 5

• Hepatic involvement: present with hepatitis or hepatic failure picture
• Neurological/psychiatric involvement: present with movement disorder symptoms which may include dysarthria (motor speech disorder), tremor, incoordination, dysphagia, drooling, dystonia, dysdiadochokinesia, rigidity etc. May also present with behavioural abnormalities such as depression, insomnia, delusions etc.
• Mixed hepatic and neurological/psychiatric
• Pre-symptomatic: from chance or tracing family tree from presenting relative

Question 6

What is the epidemiology of Wilson’s disease: Prevalence? Gender? Ethnicity? Age?

Answer 6

1 in 40,000 people. No sex or ethnic variation. Appears usually between 10 and 40.

Question 7

What are the symptoms of Wilson’s disease? (x3)

Answer 7

• HEPATIC: hepatitis, liver failure or cirrhosis. Jaundice, easy bruising from low platelets, variceal bleeding from portal hypertension, raised JVP, ascites and encephalopathy.
• NEUROLOGICAL: dyskinesia, tremor, dysarthria (slurred speech, hypokinetic, and echolalia (meaningless repetition of another’s words)), dystonia, drooling, incoordination, dysdiadochokinesia.
• PSYCHIATRIC: conduct disorder, psychosis, depression, insomnia, delusions.

Question 8

What are the signs of Wilson’s disease? (x2)

Answer 8

• HEPATIC: hepatosplenomegaly, jaundice, ascites, oedema, gynaecomastia
• EYES: Kayser-Fleischer rings (in over 99% of neurological patients, and 50-62% of hepatic patients)

Question 9

What are Kayser-Fleischer rings?

Answer 9

Green or brown, dark rings that encircle the iris due to deposition of copper in Descemet’s membrane (where cornea meets sclera).

Question 10

What risk factor in your diet predisposes Wilson’s disease?

Answer 10

Eating meat as more bioavailable copper.

Question 11

What neurological functions are spared in Wilson’s disease? (x3)

Answer 11

Normal sensation, muscle strength and reflexes.

Question 12

What are the investigations for Wilson’s disease? (x8)

Answer 12

• LFTs: raised aminotransferases, bilirubin, hypoalbuminemia.
• 24-hour urine copper: higher than 100 micrograms.
• FBC: low platelets and WBC from portal hypertension and splenic sequestration
• Slit-lamp examination: Kayser-Fleischer rings
• Blood ceruloplasmin: copper-binding protein is less than 180mg/L
• Liver biopsy: liver copper higher than 250 micrograms/g (more than 200 in neurological patients)
• MRI brain: not specific for Wilson’s; involvement of basal ganglia which is seen as increased density
• DNA testing for ATP7B mutations

Question 13

What is a slit-lamp examination?

Answer 13

High light intensity focused to shine a thin sheet of light into the eye to isolate a segment of the eye for examination.