Wilson disease is an autosomal recessive disorder in which patients accumulate a ton of copper. Let’s take a look at copper metabolism and then look into the disease in a little more detail.

People generally eat around 2-5 mg of copper a day. About half of it is absorbed in the duodenum and proximal small intestine. It is attached to albumin and histidine and dumped into the portal circulation. In the liver, the copper dissociates and is used to make enzymes and ceruloplasmin (the main form of circulating copper). Circulating ceruloplasmin eventually finds its way back to the liver, where the copper dissociates and is excreted into the bile.

Back to Wilson disease. Patients with Wilson disease have a mutation in the ATP7B gene, the product of which is a copper-transporting ATPase located on the canalicular membrane of the hepatocyte. A decrease in ATP7B protein means that copper can’t be transported into bile. It also means that ceruloplasmin production and secretion is diminished.

In the early stages of disease, copper accumulates in the liver (since it can’t be properly excreted), where it causes injury through production of reactive oxygen species. The liver damage can be minor (just some steatosis), moderate (hepatitis) or severe (massive liver necrosis). Later on, the copper accumulates to such an extent that it spills over into the blood (causing hemolysis) and travels to distant organs (especially brain and eye, but also kidney, bones and joints, and parathyroid glands). In the brain, patients often get severe atrophy of the basal ganglia; in the eye, patients often develop eye lesions called Kayser-Fleischer rings (which show up as green-brown deposits around the iris, as seen in the photo above). Urinary copper goes way up too.

Clinically, the disease varies a lot from patient to patient. It presents anywhere from childhood to middle age. The most common presenting symptoms are related to liver disease; but neuropsychiatric symptoms (behavioral changes or a Parkinson disease-like syndrome) are seen too. If you see Kayser-Fleischer rings, that helps in the diagnosis.

You’d think that the main diagnostic test would be a serum copper level – but you really can’t use that, since the amount of free copper varies a lot over the course of the disease. Tests that do help include serum ceruloplasmin (which should be low), hepatic copper quantification (which should be elevated), and urinary copper levels (which should be elevated).

Treatment usually involves long-term copper chelation; patients usually do pretty well. Patients with very severe disease may need a liver transplant (which offers the chance for a cure).