20th July 2023

Wilson’s Disease

A genetic disorder in which there is a problem with copper metabolism, causing an accumulation of copper in the body. Copper deposition occurs in the basal ganglia, cornea and liver. Akinetic-rigid syndrome +/- dyskinesia. Neurological damage can be reversible with early treatment. Treatment is with a chelating agent such as penicillamine.

Causes

It is autosomal recessive in inheritance, caused by a mutation in the protein ATP7B gene on chromosome 13q14.3. The protein codes for the transportation of excess copper into bile for excretion. Gene codes for P-type ATPase that transports copper to bile and incorporates it into cerulosplasmin.

Signs and Symptoms

These arise from the accumulation of copper in the liver and brain, causing liver disease and neuropsychiatric symptoms. Generally, those with liver issues present in childhood or teenage years. Copper deposition in the liver can lead to increased coagulopathy, lethargy, hepatic encephalopathy or portal hypertension and, as a result, other sequelae of chronic liver disease. Copper deposition in the brain causes cognitive impairment and ataxia. They can also present as symptoms of Parkinsonism. Deposition is predominantly in the basal ganglia.

Other manifestations include Kayser-Fleischer rings in the eyes, hypoparathyroidism, renal tubular acidosis type 2 or cardiomyopathy.

Diagnosis

A combination of blood tests checking the level of ceruloplasmin and copper, genetic testing, urinary copper excretion tests and liver biopsy is used.

MRI shows copper deposition in the basal ganglia giving a ‘face of the giant panda’.

Management

Reduce dietary copper intake, such as by avoiding mushrooms, liver, nuts, chocolate and dried fruit. Lifelong penicillamine is used, which is a chelating agent which binds copper and excretes it in the urine. Note its side effect of drug-induced lupus. Liver transplant is curative, although there are strict criteria by which this can be used.