Wilson's disease

see also:

• caeruloplasmin
• copper

• an autosomal recessive genetic disorder caused by a mutation in ATP7B gene in which excess copper builds up in the body, particularly in the liver, kidneys, eyes and brain (especially in the lenticular nucleus of the basal ganglia, - the putamen and globus pallidus)
• ATPB7B protein is an important component of copper homeostatic mechanisms as it transports excess copper into bile, where it is excreted in waste products
• ATP7B gene is on chromosome 13 (13q14.3) and is expressed primarily in the liver, kidney, and placenta
• the gene codes for a P-type (cation transport enzyme) ATPase that transports copper into bile and incorporates it into caeruloplasmin
• first described in 1854 by a German pathologist Friedrich Theodor von Frerichs and is named after British neurologist Samuel Wilson who described it in 1912
• occurs in 1 in 30,000 people and if untreated is eventually fatal

• onset is usually between ages 5 and 35 years
• chronic active hepatitis usually presents first
  • tiredness
  • jaundice
  • later, features of cirrhosis, splenomegaly, ascites
  • 5% present in hepatic encephalopathy with fulminant liver failure
• other features may occur
  • Kayser–Fleischer rings (KF rings) may be visible in the cornea of the eyes
  • type 2 renal tubular acidosis may occur with nephrocalcinosis and occasionally, aminoaciduria
  • hypoparathyroidism
  • infertility
  • recurrent miscarriage
  • haemolysis
  • rarely, cardiomyopathy
• half have neuro-psychiatric symptoms
  • clumsiness
  • mild cognitive deterioration
  • behavioural changes
  • migraine tends to be more common in thee patients
  • later, Parkinson's disease, seizures, depression or psychosis
    • may have a characteristic tremor described as “wing-beating tremor”

• slit-lamp to look for Kayser–Fleischer rings
• low caeruloplasmin levels
  • 80-95% have abnormally low levels
  • low levels are also found in the much more rare conditions:
    • Menkes disease
      • an X-linked recessive disorder caused by mutations in genes coding for the copper-transport protein ATP7A
      • 1 in 100,000 to 250,000 newborns; 70% inherited from the mother, 30% sporadic new mutations
    • acaeruloplasminaemia / aceruloplasminemia
      • rare autosomal recessive disorder (~ 1 in 2 million)
• low serum copper
  • this is paradoxically low as copper in the serum is bound to caeruloplasmin and as this is low so is the amount of copper
• penicillamine test in children
  • 24 hr urine collection after 500 mg oral dose of penicillamine
• liver biopsy to assess severity
• genetic testing

• low copper diet
  • avoidance of mushrooms, nuts, chocolate, dried fruit, liver, sesame seeds and sesame oil, and shellfish
• avoid using copper cooking pots
• chelating agents
• liver transplant may be indicated as a cure