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Semin Liver Dis 2011; 31(3): 245-259
DOI: 10.1055/s-0031-1286056
© Thieme Medical Publishers

Wilson Disease: Pathogenesis and Clinical Considerations in Diagnosis and Treatment

Richard Rosencrantz1 , 2 , Michael Schilsky2 , 3
  • 1Department of Pediatrics, New Haven, Connecticut
  • 2Yale New Haven Transplantation Center, New Haven, Connecticut
  • 3Division of Digestive Diseases and Section of Transplantation and Immunology, Department of Medicine and Surgery, Yale University School of Medicine, New Haven, Connecticut
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Publication History

Publication Date:
07 September 2011 (online)

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ABSTRACT

Nearly a century after Dr. Samuel Alexander Kinnier Wilson composed his doctoral thesis on the pathologic findings of “lenticular degeneration” in the brain associated with cirrhosis of the liver we know that the underlying molecular basis for this autosomal recessive inherited disorder that now bears his name is mutation of a copper transporting ATPase, ATP7B, an intracellular copper transporter mainly expressed in hepatocytes. Loss of ATP7B function is the basis for reduced hepatic biliary copper excretion and reduced incorporation of copper into ceruloplasmin. During the intervening years, there was recognition of the clinical signs, histologic, biochemical features, and mutation analysis of ATP7B that characterize and enable diagnosis of this disorder. These include the presence of signs of liver or neurologic disease and detection of Kayser-Fleischer rings, low ceruloplasmin, elevated urine and hepatic copper, and associated histologic changes in the liver. Medical therapies and liver transplantation can effectively treat patients with this once uniformly fatal disorder. The earlier detection of the disease led to the initiation of treatment to prevent disease progression and reverse pathologic findings if present, and family screening to detect the disorder in first-degree relatives is warranted. Gene therapy and hepatocyte cell transplantation for Wilson disease has only been tested in animal models but represent future areas for study. Despite all the advances we still have to consider the diagnosis of Wilson disease to test patients for this disorder and properly establish the diagnosis before committing to life-long treatment.

KEYWORDS

Wilson disease - copper - ceruloplasmin - Kayser-Fleischer rings - ATP7B

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Michael SchilskyM.D. 

Division of Digestive Diseases and Section of Transplantation and Immunology, Department of Medicine and Surgery, Yale University School of Medicine

333 Cedar Street, LMP 1080, New Haven, CT 06520

Email: michael.schilsky@yale.edu

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