Wilson disease is an inherited genetic disorder associated with abnormal copper metabolism that results in excess storage of copper, primarily in the liver and brain. Copper is an essential mineral that is absorbed into the body through the diet. It is incorporated into enzymes that play a role in the regulation of iron metabolism, formation of connective tissue, energy production at the cellular level, the production of melanin, and the function of the nervous system and brain.
Copper is absorbed in the intestines, bound to a carrier protein, and transported to the liver. The liver stores some of the copper and binds most of the rest to a protein called apoceruloplasmin to produce the enzyme ceruloplasmin. About 95% of the copper in the blood is bound to ceruloplasmin, and most of the rest is bound to other proteins, such as albumin. Only a small amount is normally present in the blood in a free (unbound) state. Excess copper is normally excreted into the bile and removed from the body in the stool. Some copper is also eliminated by the kidneys into the urine.
Wilson disease is an autosomal recessive disorder, which means it takes two altered gene copies, one inherited from each parent, to cause the disorder. Those with only one copy are carriers and can pass the mutation on to their children but do not have symptoms of the disease.
The gene mutation in Wilson disease is at the ATP7B gene. This gene is needed both to attach copper to the developing ceruloplasmin molecule and to excrete copper into the bile. An alteration in both gene copies (homozygous) leads to excess copper storage in the liver and to a decrease in ceruloplasmin in the blood. As the build-up becomes toxic, copper begins to damage the cells and tissues in the liver, spills into the blood, and begins to form deposits in other organs such as the brain and kidneys. Free (unbound) copper concentrations in the blood increase and can cause oxidative damage to cells. Those affected may have signs and symptoms associated with liver dysfunction, neurologic damage, or both. The severity of the condition depends partly upon the gene mutations present but will also vary from person to person.
About 1 in 30,000 people in the United States have Wilson disease and as many as 1 in 90 are estimated to be carriers. There are currently about 40 known normal variants of the ATP7B gene and over 260 different mutations of the ATP7B gene that have been associated with Wilson disease. Only a few of these mutations are common, however, with their prevalence varying with ethnicity throughout the world. Those affected may have two copies of the same genetic mutation or two different mutations.