Metabolic liver disease: Wilson's disease

Question 1

Definition

Answer 1

Wilson’s disease is a rare, autosomal recessive disorder of copper accumulation and toxicity.

Question 2

Epidemiology + Risk Factors

Answer 2

Adolescence: the mean age of onset is 17 years old, and the mean age of diagnosis is 20 years old
Family history: suggests inherited mutations in the ATP7B gene

Question 3

Aetiology

Answer 3

Mutations in the ATP7B gene on chromosome 13, resulting in dysfunction in ATP-mediated hepatocyte copper transport.

Question 4

Pathophysiology

Answer 4

Characterised by increased copper absorption from the small intestine and decreased hepatic copper excretion.
Dysfunction in ATP-mediated hepatocyte copper transport causes a lack of copper transport into the bile and a lack of incorporation into ceruloplasmin, resulting in reduced biliary excretion of copper = subsequent copper accumulation in hepatocytes, as well as leakage into serum causing raised free serum copper levels. The excess copper then accumulates in other tissues such as the basal ganglia, kidney, and cornea, causing oxidative damage.

Question 5

Signs and symptoms

Answer 5

Features of liver disease in children and adolescents, with the addition of neuropsychiatric symptoms in young adults
Neurological
- Behavioural and psychiatric issues: such as depression and delusions, often the first presentation
Parkinsonism: half of patients present with a tremor
- Asterixis
- Chorea
- Dysarthria
- Dementia
Hepatic
- Hepatosplenomegaly
- Hepatitis and cirrhosis
- Jaundice
- Ascites
- Asterixis and encephalopathy
Renal
- Renal tubular acidosis
- Fanconi syndrome
Ophthalmological
- Kayser-Fleischer rings: a hallmark of Wilson’s disease
Haematological
- Haemolytic anaemia

Blue nails

Question 6

Diagnosis

Answer 6

FIRST LINE =
Copper studies:
- Reduced ceruloplasmin and increased 24 hour urinary copper excretion
- Increased free serum copper but reduced total serum copper. Copper is normally bound to ceruloplasmin. Reduced ceruloplasmin means there is more free copper but a total reduction in the amount of copper in the blood
GOLD STANDARD =
- Genetic testing: ATP7B mutation
- Liver biopsy

Question 7

Treatment

Answer 7

FIRST LINE = D-PENECILLINAMINE (Cu chelation, lifelong)
CI = Trientine hydrochloride
- Diet change (low shellfish, mushroom)
Severe = liver transplant

Question 8

Complication

Answer 8

Liver failure
Renal stones
Renal failure