Wilson's Disease

• Wilson's Disease is an autosomal recessive genetic condition resulting in the excessive accumulation of copper in the body tissues, particularly in the liver.
• WD is caused by mutations in the Wilson disease protein gene on chromosome 13 (also called the ATP7B copper-binding protein). This copper-transporting protein is important in helping remove excess copper from the body via the liver
• Copper is excreted in the bile
• Wilson's disease typically presents in teenagers or young adults, it is rare for symptoms to start after 40. Wilson's disease most commonly presents due to hepatic or neurological involvement.
• Ophthalmic features:

  • Kayser-Fleischer rings: are copper deposits in Descemet’s membrane seen with slit-lamp examination. They are present in up to 95% of patients with symptomatic neurological disease but are far less common in those without neurological symptoms.
  • Sunflower cataracts: are caused by copper deposits affecting the lens, they may be diagnosed with slit-lamp examination.
• Liver involvement:

  • Asymptomatic disease (with abnormal biochemistry)
  • Acute liver failure
  • Chronic hepatitis and cirrhosis
• Neurological involvement:

  • Akinetic-rigid syndrome: slow initiation of movement (similar to Parkinson's disease)
  • Pseudosclerosis: clinical picture dominated by tremor, which is coarse and flapping
  • Ataxia: both cerebellar ataxia and acroataxia (affecting the distal portion of limbs)
  • Dystonic syndrome: slow, repetitive, involuntary muscle contractions
• Psychiatric:

  • Behavioural changes (particularly younger patients)
  • Lability of mood
  • Impulsiveness
  • Sexual exhibitionism
  • Decline in academic performance
  • Psychotic features
  • Depression
• Can present as haemolytic anaemia - coombs negative
• Other manifestations:

  • Renal - renal tubular acidosis
  • Rheumatology - osteoarthritis, myopathy
  • Obstetric - miscarriages, infertility
• Basic investigations:

  • decreased Serum caeruloplasmin - acute phase reactant and the main carrier of copper in the blood
  • Decreased serum copper - but may be elevated in acute liver failure
  • Raised serum free copper (not bound to serum caeruloplasmin)
  • 24-hour urinary copper - reflects the unbound serum free copper, tends to be elevated
  • Slit lamp exam - Kayser-Fleischer rings
• Further investigations:

  • Liver biopsy - required if non invasive tests are not diagnostic or to rule out other conditions
  • MRI/CT head - may reveal changes in the basal ganglia - characteristic 'face of the giant panda' seen in a minority of cases
  • Genetic testing
• General management:

  • Counselling
  • Lifestyle - especially avoiding toxic drugs and alcohol
  • Follow up and lifelong monitoring
• Pharmacological (copper chelation):

  • D-Penicillamine: first line. Chelates copper and promotes its urinary excretion. Has severe side effects. Neurological symptoms can worsen at the start of treatment.
  • Trientine: also a chelation agent, promoting urinary excretion. May be used for those that do not tolerate D-penicillamine
• Transplant may be required in patients presenting with acute liver failure or decompensated cirrhosis.