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Wilson’s disease is a human copper storage disease. Wilson’s results in the accumulation of toxic levels of copper in mainly the liver and secondarily in other organs such as the kidneys, brain, and cornea. The disease is caused by a mutation in the ATP7B gene, which codes for a protein that facilitates the incorporation of copper into proteins (such as ceruloplasmin) and also the transportation of copper into vesicles that allow it to be secreted in bile.1 The critical effect of a mutation in ATP7B is diminished copper secretion into bile, which leads to excess copper accumulation in the hepatocyte. The disease related to this defect therefore involves toxicity to the liver with clinical disease that may range from abnormal liver function tests to fulminant hepatic failure and cirrhosis.

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Wilson’s is an autosomal recessive disease with an estimated incidence of 1:30,000 live births internationally.2 The most common presentation is in the second decade of life with hepatic or hematologic symptoms (40–60%). The remaining patients present with neurologic (~30%) or psychiatric (10%) symptoms in their third or fourth decade.2

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In normal human copper metabolism, the dietary intake and absorption of copper is in excess of physiologic needs. The estimated daily copper requirement for an adult is 1.3–1.7 mg, whereas the normal daily Western copper intake is 2–5 mg of copper.3,4 The estimated efficiency of copper absorption in the stomach and small intestine is approximately 40–60%. Therefore, the amount of copper absorbed by the intestine and retained in the body must be regulated to prevent accumulation of excess copper—which is toxic. The main regulatory system for maintaining copper balance in the body is the excretion of up to 80% of absorbed copper in the bile5,6 (Figure 25–1). Up to 1.2–1.7 mg/day of copper is excreted in the bile daily.6,7 There are also several chemical factors that impair intestinal copper absorption, such as excess zinc or ascorbic acid.8–10

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FIGURE 25–1
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Copper metabolism in humans (adapted from Ref.7).

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Dietary copper is absorbed into the small intestine epithelial cells where it complexes either to the protein metallothionein or to amino acids for transport into the portal circulation. Metallothionein also forms complexes with zinc and cadmium, though less strongly than copper. Zinc stimulates metallothionein synthesis in the intestinal cell. In doing so, it promotes retention of metallothionein-bound copper in the enterocyte that will then be excreted in the feces when the enterocyte is shed.11 It is on this basis that zinc was postulated to reduce intestinal copper absorption and became a modality of treatment for Wilson’s.

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Once in the portal circulation, the copper complexes to albumin or amino acids with only a small fraction remaining “free.” A copper transporter (hCTR) for albumin-bound copper then transports the copper ...

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