27B. Wilson’s disease

From greek.doctor

Wilson disease is an autosomal recessive disorder of copper metabolism characterised by the toxic accumulation of copper in the liver and central nervous system that may present with hepatic, neurologic and/or psychiatric symptoms.

Symptoms can begin any time in the age of 5 – 35 years.

Pathomechanism

A mutation in the ATP7B gene, a copper transporter causes decreased copper excretion and decreased incorporation of copper into apoceruloplasmin, thereby causing increased free serum copper. This causes copper to accumulate in the liver, CNS, cornea, kidneys, etc.

Clinical features

The patient may experience any combination of hepatic, psychiatric, and neurological symptoms.

  • Hepatic symptoms
    • Jaundice
    • Ascites
    • Acute liver failure
    • Chronic hepatitis
  • Psychiatric symptoms
    • Dementia
    • Depression
    • Personality change
  • Neurological symptoms
    • Parkinsonism
    • Dystonia
    • Dysarthria
    • Flapping tremor
    • Chorea

Green-brown rings on the periphery of the iris, called Kayser-Fleischer rings, are pathognomic for the disease and occurs in all cases.

Diagnosis and evaluation

Diagnosis is based on elevated serum copper, decreased serum ceruloplasmin, and increased urinary copper excretion. MRI-SWI shows deposition of metal in the brainstem.

Genetic testing can confirm the diagnosis.

Treatment

Treatment must begin urgently to reduce irreversible consequences. Liver symptoms improve first, while neuropsychiatric symptoms can take up to 3 years to improve.

Treatment is by a copper chelator, either trientine or penicillamine. Initially given in high doses to reduce the copper levels to normal, then given lifelong to maintain copper levels in the normal range.