Phenotypes and Chronic Organ Damage May Be Different among Siblings with Wilson's Disease

摘要

Background and Aims:Cloning of ATP7B provided evidence that Wilson's disease is a hepatic copper toxicosis with a variety of extrahepatic complications.Affected siblings with the same genetic background and exposure to similar environmental factors may be a good model for the study of genotype-phenotype correlation.Methods:Twenty-three affected siblings in 11 families were selected from a database.The first phenotypes were determined according to the international proposal.The final types of chronic organ damage were re-evaluated for life-long management.Results:Phenotypes were identical in 5 of the families and different in 6 of the families.The acute hepatic phenotype H1 was found in 3 younger siblings and 1 older sibling.All survived an acute episode of hemolysis with underlying chronic liver disease.One also presented complication with neurological disease.The neurological phenotype N1 with neuropsychiatric symptoms and hepatic disease was found in 2 aged siblings of 1 family,in an older sibling in 3 families and in the oldest sibling in 1 family.Phenotypes in siblings were mainly split by either H1 occurring in random order or age-dependent N1.Types of chronic organ damage were identical in 8 of the families and different in 3 of the families.The same combination of chronic liver disease was found in 6 families and chronic liver disease complicated with neurological disease in 2 families.Split organ damage in siblings was found when an older sibling was complicated by neurological disease.There was no reverse combination of a younger sibling being complicated by neurological disease in any of the families.Conclusion:Phenotype combinations of siblings were mainly modified by externally-induced hemolytic episodes,while chronic organ damage in siblings was split by age-dependent neurological complications.