The accumulation of excess copper in the liver is toxic in humans and other mammals and may lead to hepatitis, fulminant hepatic failure, cirrhosis, and death. Of the several human copper storage diseases that have been described, the molecular basis of only Wilson's disease is understood, with the discovery of the Wilson's disease gene (ATP7B) in 1993. The therapeutic success using oral copper chelating agents and zinc therapy makes Wilson's disease one of the few treatable metabolic liver diseases. In cases with a fulminant presentation or advanced disease at diagnosis, copper chelation is ineffective and liver transplantation is lifesaving. Indian childhood cirrhosis (ICC) has been defined as a copper storage disorder affecting children primarily of Indian descent and evolving to cirrhosis and death before age 3–4 years without treatment. Children from North America, Asia, Austria, Germany, and other countries have been described with a similar condition, which has been termed idiopathic copper toxicosis (ICT). In this chapter, copper physiology and mechanisms of copper hepatotoxicity are reviewed, followed by descriptions of the major copper storage diseases of childhood.
COPPER ABSORPTION AND METABOLISM
The normal adult Western diet contains 2–5 mg/d of copper. The efficiency of copper absorption in adults ranges from 55–75% , with higher absorption at lower intakes [1, 2] (Figure 26.1). Foods containing high amounts of copper include unprocessed wheat, dried beans, peas, shellfish (particularly oysters), chocolate, liver, and kidney. The estimated daily copper requirement for adults is approximately 1.3–1.7 mg .