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Wilson’s Disease

by | 31 May, 2020

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Introduction

Wilson’s disease is an autosomal recessive disorder in which copper accumulates in tissues.

Epidemiology

A rare disease that approximately affects 1 in 100,000

Causes

A mutation in gene ATP7B on chromosome 13 leads to Wilson’s disease. Many mutations are possible, so genetic screening has limited use.

Pathophysiology

Normally dietary copper is absorbed from the stomach and small intestine and excreted mainly via bile.

Most Wilson’s disease patients have a failure of synthesis of caeruloplasmin, thereby reducing copper excretion. The amount of copper at birth is normal but increases steadily later in life.

The organs most affected are:

  1. Liver
  2. Basal ganglia of the brain
  3. Eyes
  4. Kidneys
  5. Skeleton

Clinical features

Symptoms usually arise between the ages of 5 and 45.

Hepatic disease occurs predominantly in childhood and early adolescence. Wilson’s disease should be considered in any patient under the age of 40 with recurrent acute hepatitis or chronic liver disease.

Liver disease

Can initially present as fatigue increased bleeding tendency, confusion or portal hypertension.

Recurrent episodes of acute hepatitis can occur and may progress to fulminant liver failure. The latter is characterised by liberation of free copper into the bloodstream, causing haemolysis and renal tubulopathy.

Chronic hepatitis can also develop and eventually presents with cirrhosis. Liver failure and portal hypertension may also occur.

Neurological disease

Typically develops after the onset of liver disease but can be prevented with appropriate treatment.

Clinical features are mostly extrapyramidal in nature:

  • Tremor
  • Choreoathetosis
  • Dystonia
  • Parkinsonism
  • Dementia

Other organs affected

Eyes: Kayser-Fleischer rings – copper deposition in cornea producing brown-yellow discolouration of the iris. Seen in 60% of patients

Kayser Fleischer ringArrow
Kayser-Fleischer ring: Brown ring around iris as a result of copper deposition

Kidneys: Renal tubular necrosis

Heart: Cardiomyopathy

Endocrine: Hypoparathyroidism, infertility, recurrent abortions

Investigations

The most routinely used tests for diagnosing Wilson’s disease are bloods and urine, although liver biopsy can also be used.

  • Bloods:
    • Low caeruloplasmin – the best lab clue for diagnosis
    • Low serum copper (as it is transported by caeruloplasmin)
  • Urine: High urinary copper excretion; usually exceeds 1.6 µmol/24 hours.
  • Liver biopsy: typically shows high amounts of copper in the liver. However, chronic cholestasis can also produce a similar picture.

Management

Management options include drugs, transplant, dietary changes and physical therapy.

Drugs

Penicillamine is the drug of choice as it is a copper-binding agent that leads to cupiuresis. Following remission, the dose can be decreased. Treatment is lifelong. It should be noted that penicillamine should not be abruptly stopped as this may precipitate acute liver failure.

Alternatives to penicillamine include trientine and zinc.

Transplant

Liver transplant is indicated for fulminant liver failure or advanced cirrhosis. The treatment has an excellent prognosis.

Dietary changes

A diet low in copper should be encouraged. Patients should avoid mushrooms, nuts, chocolate, dried fruit and shellfish.

Physical therapy

Indicated for patients with neurological symptoms e.g. ataxia, dystonia

Genetic screening

Family members of patient with HHC should be offered screening for the condition.

Prognosis

Early detection allows patients to lead relatively normal lives. However, neurological damage is irreversible.

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