Wilson Disease Mayo Clinic Proceedings Mounif El-Youssef, MD  Mayo Clinic Proceedings  Volume 78, Issue 9, Pages 1126-1136 (September 2003) DOI: 10.4065/78.9.1126 Copyright © 2003 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 1 Pathway of copper metabolism. The bar represents the metabolic abnormality of Wilson disease. In the absence of normal ATP7B, intracellular trafficking of copper is inadequate, resulting in copper accumulation and increased degradation of the apoceruloplasmin form of the protein and subsequent low serum level. Excess copper eventually saturates the liver and other organs. Mayo Clinic Proceedings 2003 78, 1126-1136DOI: (10.4065/78.9.1126) Copyright © 2003 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 2 Schematic representation of the transport mechanism of copper in the hepatocyte. The metal is transported into the canalicular membrane with the help of the ATP7B molecule from the trans-Golgi. Copper in the cytosol is incorporated into apo-ceruloplasmin for transportation to various enzymes and for plasma secretion. In the absence of normal transport, the copper is not excreted into bile, and ceruloplasmin is rapidly metabolized, leading to low serum levels and copper toxicosis. Mayo Clinic Proceedings 2003 78, 1126-1136DOI: (10.4065/78.9.1126) Copyright © 2003 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 3 Distribution of hepatic and neurologic manifestations of Wilson disease by age. Note that hepatic manifestations predominate in the pediatric age group in contrast to the neurologic manifestations in individuals older than 18 years. Mayo Clinic Proceedings 2003 78, 1126-1136DOI: (10.4065/78.9.1126) Copyright © 2003 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 4 Distribution of hepatic presentations of Wilson disease. Mayo Clinic Proceedings 2003 78, 1126-1136DOI: (10.4065/78.9.1126) Copyright © 2003 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 5 Features typical of chronic hepatitis with portal inflammation by lymphocytic infiltration and piecemeal necrosis spilling into the parenchyma beyond the limiting plate. There is evidence of lobular disarray with hepatocyte cords that seem to be disrupted. Mayo Clinic Proceedings 2003 78, 1126-1136DOI: (10.4065/78.9.1126) Copyright © 2003 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 6 Steatosis and steatohepatitis associated with the accumulation of fat in a patient with Wilson disease. It is presumed that mitochondrial injury causes disruption of fatty acid oxidation with resultant lipid accumulation inside the hepatocytes. Mayo Clinic Proceedings 2003 78, 1126-1136DOI: (10.4065/78.9.1126) Copyright © 2003 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 7 Established cirrhosis in a patient with Wilson disease. Note the extensive fibrosis bridging from one portal area to the next. Mayo Clinic Proceedings 2003 78, 1126-1136DOI: (10.4065/78.9.1126) Copyright © 2003 Mayo Foundation for Medical Education and Research Terms and Conditions

Figure 8 P-type adenosine triphosphatase (ATPase) is responsible for the binding and transport of copper. Note the 6 copper-binding domains, the adenosine triphosphate (ATP)–binding domain, the phosphorylation domain, and the channel domain. Mayo Clinic Proceedings 2003 78, 1126-1136DOI: (10.4065/78.9.1126) Copyright © 2003 Mayo Foundation for Medical Education and Research Terms and Conditions