Recognition and Treatment of Neurologic Wilson's Disease
Recognition and Treatment of Neurologic Wilson's Disease
Wilson's disease is an autosomal recessive disease, with a prevalence of ~ 4 per million, that occurs when a patient carries mutations in both copies of their ATP7B gene. ATP7B is a 1411 amino acid copper transporting P-type transmembrane ATPase that is highly expressed in the liver, kidney, and placenta. Mutational analysis has identified over 300 different Wilson's disease mutations throughout the ATP7B gene. Most individuals are compound heterozygotes.
Humans, including Wilson's disease patients, take in ~ 1.0 mg of copper per day in their diet, and have a requirement for only ~ 0.75 mg. The normal mechanism for elimination of excess copper is excretion in the bile for loss in the stool. Dietary copper is absorbed in the stomach and duodenum and transported via the portal vein to the liver, the main organ controlling copper regulation. Copper is absorbed into hepatocytes and transported to ATP7B. The normal function of ATP7B appears to be incorporation of copper into ceruloplasmin and secretion of copper into bile. As a result of Wilson's disease mutations, the liver is not capable of excreting excess copper into the bile, and a positive copper balance, averaging ~0.25 mg/d, is established. Copper accumulates over time, first in the liver and then in other parts of the body, such as in the brain. The damage from excessive copper appears to be oxidant in nature.
Molecular Genetics and Pathogenesis
Wilson's disease is an autosomal recessive disease, with a prevalence of ~ 4 per million, that occurs when a patient carries mutations in both copies of their ATP7B gene. ATP7B is a 1411 amino acid copper transporting P-type transmembrane ATPase that is highly expressed in the liver, kidney, and placenta. Mutational analysis has identified over 300 different Wilson's disease mutations throughout the ATP7B gene. Most individuals are compound heterozygotes.
Humans, including Wilson's disease patients, take in ~ 1.0 mg of copper per day in their diet, and have a requirement for only ~ 0.75 mg. The normal mechanism for elimination of excess copper is excretion in the bile for loss in the stool. Dietary copper is absorbed in the stomach and duodenum and transported via the portal vein to the liver, the main organ controlling copper regulation. Copper is absorbed into hepatocytes and transported to ATP7B. The normal function of ATP7B appears to be incorporation of copper into ceruloplasmin and secretion of copper into bile. As a result of Wilson's disease mutations, the liver is not capable of excreting excess copper into the bile, and a positive copper balance, averaging ~0.25 mg/d, is established. Copper accumulates over time, first in the liver and then in other parts of the body, such as in the brain. The damage from excessive copper appears to be oxidant in nature.
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