Wilson disease is an autosomal recessive disorder of copper metabolism. Copper that the liver cannot excrete into the bile accumulates first in the hepatocytes and later in the brain, kidney and cornea, where its toxicity produces the disease. The fault lies in ATP7B, the copper-transporting ATPase that both excretes copper into bile and loads ceruloplasmin with copper. Kinnear Wilson first described the condition in the 1910s as a familial disorder in which neurological disease accompanied cirrhosis.
Copper itself is an essential mineral, needed by several enzymes, and the diet supplies it well above daily need, so the body normally keeps the surplus moving out. Two genetic disorders disturb that balance: Menkes disease, an X-linked defect of intestinal absorption that causes generalised copper deficiency, and Wilson disease, in which copper overloads the body.
Choose a route through this family
If you are new to the topic, start with how the body normally handles copper and what goes wrong when it cannot.
- Copper Physiology and Transport: how copper is absorbed, carried to the liver, handed to the enzymes that need it, and kept non-toxic by binding proteins.
- Pathophysiology of Wilson Disease: the ATP7B gene and its inheritance, the two jobs the transporter performs, and how retained copper injures the hepatocyte.
Recognition comes next: how the disease announces itself, and how it is confirmed.
- Clinical Manifestations of Wilson Disease: the hepatic, neurological, psychiatric and ocular ways the disease appears, and how it mimics commoner conditions.
- Diagnosis of Wilson Disease: the biochemical tests and their pitfalls, the thresholds that support the diagnosis, genetic testing and the screening of relatives.
Finally, the drugs and surgery that reverse the copper overload.
- Treatment of Wilson Disease: the chelators and zinc salts that restore a negative copper balance, liver transplantation, monitoring, and the outlook on treatment.