Wilson's Disease

Question 1

Pathology

Genetics

Answer 1

Wilson disease is the excessive accumulation of copper in the body and tissues.

It is caused by a mutation in the “Wilson disease protein” on chromosome 13.

The Wilson disease protein also has the catchy name “ATP7B copper-binding protein” and is responsible for various functions, including the removal of excess copper in the liver.

Genetic inheritance is autosomal recessive.

Question 2

Clinical Features

Answer 2

Most patients with Wilson disease present with one or more of:

• Hepatic problems (40%): Copper deposition in the liver leads to chronic hepatitis and eventually liver cirrhosis.
• Neurological problems (50%): range from concentration and coordination difficulties to dysarthria (speech difficulties) and dystonia (abnormal muscle tone). Copper deposition in the basal ganglia leads to Parkinsonism (tremor, bradykinesia and rigidity). Motor symptoms are often asymmetrical in Wilson disease.
• Psychiatric problems (10%)

Other clinical features:
- KAYSER-FLEISCHER rings in cornea (deposition of copper in Descemet’s corneal membrane). These are brownish circles surrounding the iris. They can usually be seen by the naked eye but proper assessment is made using slit lamp examination.

• Haemolytic anaemia
• Renal tubular damage leading to renal tubular acidosis
• Osteopenia (loss of bone mineral density)

Question 3

Diagnosis

Initial vs Gold Standard

Answer 3

The initial investigation of choice is SERUM CAERULOPLASMIN = A LOW serum caeruloplasmin is suggestive of Wilson disease. This is the protein that carries copper in the blood. It can be falsely normal or elevated in cancer or inflammatory conditions. It is also not specific to Wilson disease.

Liver biopsy for liver copper content is the definitive gold standard test for diagnosis.

Diagnosis can also be established if the 24-hour urine copper assay is sufficiently elevated.

Alternatively there are scoring systems that take in to account various features and laboratory tests to establish a diagnosis of Wilson disease.

Other investigations:

Low serum copper
Kayser-Fleischer rings
MRI brain shows nonspecific changes

Question 4

Management

Answer 4

Treatment is with copper chelation using:

• Penicillamine
• Trientene