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
REFERENCES
http://www.hgmd.cf.ac.uk/ac/index.php Accessed June 6, 2011 http://www.wilsondisease.med.ualberta.ca/index.asp Accessed June 6, 2011
michael.schilsky@yale.edu
