22nd July 2023

Wilson’s disease

Background

Wilson’s disease is a rare autosomal recessive condition that results in the accumulation of copper. There are several associated mutations of the ATP7B gene, on chromosome 13, which affects the ability of the liver to excrete copper.

High levels of free copper causes widespread toxicity. Typically, people with Wilson’s disease have either hepatic involvement or neurological/psychiatric manifestations; however, occasionally both may be present.

Assessment and diagnosis

Those with liver manifestations can present with hepatitis, cirrhosis or liver failure.

Neurological and psychiatric symptoms include tremor, ataxia, dysarthria, dystonia, depression, poor memory, disinhibition, and other unusual behaviours.

Examination findings may include Kayser-Fleischer rings; however, these are more commonly found in the neurological manifestation of the disease, rather than hepatic. Neurological examination may identify signs in keeping with movement disorder; however, sensation, strength and reflexes should be normal.

Investigations should include LFTs, 24-hour urinary copper measurement, and ceruloplasmin.

Where the diagnosis is not certain, a liver biopsy with quantitative assay of copper can be done as a definitive diagnostic test.

For those with neurological involvement, MRI brain imaging can be helpful and may show increased density in the basal ganglia and the ‘face of the giant panda’ sign in the midbrain. Neither of these findings are specific for Wilson’s disease, however.

Management

Wilson’s disease is a treatable genetic condition, and therefore, timely diagnosis is important. Medical treatment aims to eliminate copper and prevent re-accumulation. Current recommended medications are zinc, which blocks copper resorption in the gut, and trientine, which increases urinary copper excretion. Older treatments used for Wilson’s disease include d-penicillamine; however, this can worsen neurological symptoms and may have severe adverse effects.

For those with liver involvement, the severity of hepatic disease should be established with the Nazer score (see BMJ Best Practice, in References section), as this will guide whether the patient can be managed with pharmacological therapy or whether they require consideration for a liver transplant. Dietary advice is also important; for example, limiting the intake of liver and shellfish in the initial stages of treatment, due to their high copper content.