Wilson disease: new insights into pathogenesis, diagnosis, and future therapy.
Wilson disease is caused by disease-specific mutations of the copper transporting ATPase, ATP7B. The diagnosis is established by clinical and biochemical means, though advances in molecular diagnostics will someday permit de novo diagnosis. The patient may present with hepatic, neurologic, or psychiatric symptoms, or a combination of these. Both environmental and extragenic effects contribute to the varied phenotypic presentations of this disease. Patients can be treated effectively with chelating agents or zinc salts, or with liver transplantation. Liver cell transplant and gene therapy offer potential cures for this disorder, but at present only data from preclinical studies on animal models are available. Future advances in immunotolerization and gene therapy will likely enable human trials for treatment of this disorder and other genetic disorders of hepatic metabolism.
Schilsky
Michael L
ML
Center for Liver Disease and Transplantation, The New York Weill Cornell Medical Center, 525 East 68th Street, Box #98 M203, New York, NY 10021, USA. mls2003@med.cornell.edu
D000251:Adenosine Triphosphatases / Q000235:genetics*; D027682:Cation Transport Proteins / Q000235:genetics*; D017690:Cell Transplantation / Q000379:methods; D000073840:Copper-Transporting ATPases; D005260:Female; D005544:Forecasting; D020022:Genetic Predisposition to Disease; D015316:Genetic Therapy / Q000379:methods*; D022781:Hepatocytes / Q000637:transplantation*; D006527:Hepatolenticular Degeneration / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000628:therapy*; D006801:Humans; D016031:Liver Transplantation / Q000379:methods; D008297:Male; D010396:Penicillamine / Q000627:therapeutic use*; D011379:Prognosis; D018570:Risk Assessment; D012720:Severity of Illness Index; D016019:Survival Analysis; D016896:Treatment Outcome
D027682:Cation Transport Proteins; D000251:Adenosine Triphosphatases; D000073840:Copper-Transporting ATPases; D010396:Penicillamine