Wilson's Disease: Inherited Disease of Toxic Copper Accumulation

Due to a failure of copper excretion in the liver, toxic levels of copper build up and cause damage to the liver and central nervous system.

Wilson's disease or Wilson disease or hepatolenticular degeneration is an inherited disorder involving toxic accumulation of copper in the liver and the central nervous system (CNS). Accumulation in the CNS usually occurs in the sites of the basal ganglia and globus pallidus. These symptoms are all due to a failure of copper excretion by the liver.

Genetics of Wilson Disease

The incidence of Wilson's disease is 3 in 100 000. It is an autosomal recessive disorder where there is a mutation on the ATP7B gene, an ATPase, which is a copper transporter on chromosome 13. There are many known mutations but the most common is HIS1069GLU which is most common in the European population.

Clinical Features of Wilson's Disease

Children can present with liver disease and this can be expressed as fulminant liver failure, hepatitis, or cirrhosis. In young adults, one can see CNS signs such as tremor, dysarthria, dysphagia, dyskinesias, dystonias, dementia, and parkinsonism. They can also develop affective features such as depression or mania, labile emotions, fluctuating libido and personality changes. With regards to their cognition, memory can decrease and problem solving can become increasingly difficult. A famous sign of Wilson disease is the presence of Kayser-Fleischer rings, which are copper deposits in the iris.

Tests and Diagnosis of Wilson Disease

In patients with Wilson's disease, serum copper and serum caeruoplasmin are usually decreased. One can test with a 24 hour urinary copper excretion. Molecular testing is available to look for mutations in the ATP7B gene and to make a definitive diagnosis. Magnetic resonance imaging (MRI) is often used to look for signs of basal ganglia degeneration.

Management and Treatment of Wilson's Disease

Patients with Wilson's disease are on lifelong penicillinamine.

Penicillinamine is a metabolite of peniciliin but it has no antibiotic properties. It is a chelating agent that binds to accumulated copper and is then eliminated through the urine. Some possible side effects of penicillinamine are nausea, rash, low white cell count, anemia, thrombocytopenia, and haematuria.

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