Wilson’s disease: the ATP7B copper transport defect
Wilson’s disease is an inherited condition in which a faulty ATP7B copper pump impairs the excretion of copper into bile, so copper builds up in the liver, brain and eyes.
Remember
Abnormal liver tests in a young person, together with movement problems or behavioural change, should make you think of Wilson’s disease: a faulty ATP7B copper pump impairs the excretion of copper from the liver into bile.
Wilson’s disease is inherited in an autosomal recessive way, which means a person needs a faulty copy of the gene from each parent. The gene is ATP7B, and it codes for a copper-transporting ATPase, a pump in liver cells that uses energy from ATP to move copper.
The pump has two jobs. Moving surplus copper into bile is how the body gets rid of it, and the pump also loads copper onto caeruloplasmin, a copper-carrying protein made by the liver. When the pump fails, less copper is excreted into bile and less is loaded onto caeruloplasmin, so its level in the blood is usually low, but it can be normal.
Copper then accumulates, first in the liver, causing inflammation, then scarring and eventually cirrhosis. It also spills into the blood and is deposited in other organs. In the brain it causes tremor and other movement problems, and psychiatric or behavioural change. In the cornea (the clear dome at the front of the eye) it forms the Kayser-Fleischer ring, a gold, greenish-gold or brownish ring that appears to encircle the iris (the coloured part of the eye).
A slit lamp, a microscope with a bright, narrow beam of light, is used to look for the ring. A ring is nearly diagnostic when it comes with typical movement problems or a low caeruloplasmin, but it is not present in every patient, and a normal eye examination does not rule the diagnosis out.
Key facts
- Inheritance
- Autosomal recessive, with the gene on chromosome 13.
- Presentation
- Liver disease, neurological or psychiatric features, or a mixture, with symptoms usually developing between ages 5 and 35.
- Caeruloplasmin
- Usually low because copper is not loaded onto it, but it can be normal and may be low in other liver disorders.
- Urine copper
- The 24-hour urinary copper excretion is usually above 100 micrograms a day, against 30 or less normally.
- Kayser-Fleischer ring
- Usually absent in children under 6 years, and found less often when the disease presents with liver problems.
- Treatment
- A low-copper diet plus a chelating drug (one that binds copper so it can be removed), such as penicillamine or trientine.
Exam traps
- Too much copper absorbed from the diet is not the cause of Wilson’s disease, because the underlying defect is a failure to excrete copper into bile.
- A low caeruloplasmin is not a separate primary cause of Wilson’s disease, because it follows from the transporter defect when copper is not loaded onto the protein.
- Wilson’s disease is the opposite of Menkes disease, a copper deficiency state seen in male infants: in Wilson’s disease copper is retained and accumulates.
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