Wilson's Disease

Question 1

Define Wilson’s Disease

Answer 1

Wilson’s disease is an autosomal-recessive disease of copper accumulation and toxicity caused by a defect in an enzyme involved in the biliary excretion of excess copper.

Question 2

Aetilogy/Risk Factors

Answer 2

• There is a mutation in the ATP7B protein
• Reduced incorporation of copper into apoceruloplasmin so there is decreased serum ceruloplasmin
• When ceruloplasmin is bound to copper, it is called holoceruloplasmin. When it is not bound to copper, it is called apoceruloplasmin.
• ↑ free serum copper → accumulation in the liver, cornea, CNS (basal ganglia, brain stem, cerebellum)
• This is a disease of young people

Question 3

Presenting symptoms & Physical signs of Wilson’s Disease

Answer 3

This condition is also known as Hepatolenticular Degeneration (basal ganglia/extrapyramidal system and hepatic deposition)

BRONZE PIGMENTATION of the skin

HEPATIC:

• Hepatosplenomegaly
• Portal hypertension
• Abdominal pain
• Jaundice
• Ascites
• Hepatic encephalopathy

Kayser-Fleischer rings:

• Cu accumulation in Descemet membrane of the cornea that results in 1–2 mm wide, green-brown rings in the periphery of the iris
• 98% of patients who also have neurological symptoms

NEURO/PSYCHIATRIC (normal sensation, power, reflexes):

• Dysarthria
• Dystonia
• Parkinsonism
• Tremor (fine, intentional, wing-beating)
• Behavioral changes (e.g., depression, irritability, psychosis)
• Dysdiadochokinesis
• Cognitive impairment

Question 4

Investigations for Wilson’s Disease

Answer 4

• 1st Line –> LFTs: abnormal (raised transaminase, reduced albumin e.t.c.)
• 24 hour urine Copper: Raised
• Slit-lamp examination: Kayser-Fleischer rings
• Serum ceruloplasmin: LOW
  
  • As ceruloplasmin carries the Cu in blood, serum total copper is decreased HOWEVER free Cu is increased

Question 5

Management

Answer 5

Penicillamine (copper chelator)