Gastrointestinal System >
Wilson’s Disease

“An autosomal recessive disorder characterised by an error in copper metabolism and accumulation. Sometimes referred to as hepatolenticular degeneration”

Risk Factors
  • The only known risk factor is a family history of Wilson’s disease
Aetiology
  • A mutation in the ATP7B gene on chromosome 13 results in a defective transporter protein called P-type adenosine triphosphatase (ATPase)
Pathophysiology
  • Normally, copper is absorbed by the small intestine and transported to the liver for storage and processing.
  • ATP7B is responsible for linking copper to caeruloplasmin so that it can be released into the bloodstream or secreted into bile.
  • Both of these functions are impaired in Wilson’s disease, leading to abnormal excretion and accumulation of copper
Clinical Presentation
  • Liver:
    • Manifestations range from acute liver injury (coagulopathy, no signs of encephalopathy), cirrhosis, and eventually fulminant liver failure (rapid development of coagulopathy and encephalopathy in a patient without known prior liver disease).
    • Signs and symptoms of liver disease include jaundice, abdominal pain, oesophageal varices (caused by portal hypertension), splenomegaly, ascites, haemolytic anaemia, deranged coagulation, and signs of hepatic encephalopathy such as confusion, coma, seizures, and life-threatening swelling of the brain.
  • Neuropsychiatric:
    • Initially – mild cognitive deterioration, clumsiness and behavioural changes.
    • Neurological symptoms – movement disorders such as parkinsonism (cogwheel rigidity, bradykinesia) with or without tremors, dyskinesia and ataxia.
    • Psychiatric symptoms (rarely manifest on their own) – depression, anxiety disorders, psychosis with or without hallucinations, and dementia.
  • Ophthalmology:
    • Kayser-Fleischer rings (seen in 95% of patients) – copper deposition in Descemet’s membrane. These appear dark brown, golden, or reddish-green, are 1-3mm wide, and appear at the corneal limbus.
    • Sunflower cataracts are characterised by brown or green pigmentation of the anterior and posterior lens capsule. Neither of these usually cause significant visual loss.
  • Renal:
    • Associated with Fanconi syndrome – a syndrome of inadequate reabsorption in the proximal renal tubules. Type 2 renal tubular acidosis is a part of Fanconi syndrome. It is a disorder of bicarbonate handling (excessive bicarbonate is secreted in the urine), leading to calcium accumulation in the kidneys (nephrocalcinosis), weakening of bones (due to loss of calcium and phosphate), and occasionally aminoaciduria.
  • Rheumatology:
    • Arthritis, chondrocalcinosis, and osteopenia due to hypoparathyroidism
  • Cardiac:
    • Cardiomyopathy is a rare but recognised problem – can lead to heart failure and cardiac arrhythmias
Investigations
  • Check serum caeruloplasmin – reduced levels may be diagnostic but it is an acute-phase protein so levels will be elevated in infection or inflammatory states
  • Check 24-hour urinary copper excretion – levels of >100mcg are suggestive
  • Other blood tests – LFTs such as ALT and AST are normally deranged due to liver injury, with or without the presence of anaemia
  • Liver biopsy – this is only performed if diagnosis is uncertain. Can be used to measure the hepatic copper concentration which will be raised in Wilson’s.
  • MRI or CT  – may be used to image the basal ganglia
Management
  • Principles of treatment include patient education and removal of excess copper:
    • offer dietary advise e.g. avoidance of food with high copper content
    • give a chelating agent e.g. lifelong penicillamine ± zinc ± trientine
    • consider liver transplantation in severe liver disease.
  • Side effects of penicillamine include nausea, rash, bone marrow suppression and lupus-mimicking symptoms
Complications

If left untreated, Wilson’s disease becomes progressively worse and is eventually fatal. Liver and neurological damage that occurs prior to treatment may improve but it is often permanent

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