Review Diagnosis and phenotypic classi®cation of Wilson disease 1 FerenciP,CacaK,LoudianosG,Mieli-VerganiG,TannerS,SternliebI, Schilsky M, Cox D, Berr F. Diagnosis and phenotypic classi®cation of Wilson disease 1 . Liver International 2003: 23: 139±142. ß Blackwell Munksgaard, 2003 Wilson disease is an inherited autosomal recessive disorder of hepatic copper metabolism leading to copper accumulation in hepatocytes and in extrahepatic organs such as the brain and the cornea. Originally Wilson diseasewasdescribedasaneurodegerativedisorderassociatedwithcirrhosis oftheliver.Later,Wilsondiseasewasobservedinchildrenandadolescents presenting with acute or chronic liver disease without any neurologic symptoms. While diagnosis of neurologic Wilson disease is straightforward, itmaybequitedif®cultinnon-neurologiccases.Uptonow,nosingle diagnostictestcanexcludeorcon®rmWilsondiseasewith100%certainty.In 1993,thegeneresponsibleforWilsondiseasewasclonedandlocalizedon chromosome13q14.3(MIM277900)(1,2).TheWilsondiseasegeneATP7B encodesaP-typeATPase.Morethan200diseasecausingmutationsofthis genehavebeendescribedsofar(3).Mostofthesemutationsoccurinsingle families,onlyafewaremorefrequent(likeH1069Q,3400delCand2299insC inCaucasian(4±6)orR778LinJapanese(7),ChineseandKoreanpatients). Studies of phenotype-genotype relations are hampered by the lack of standard diagnostic criteria and phenotypic classi®cations. To overcome thisproblem,aworkingpartydiscussedtheseproblemsindepthatthe 8th International Meeting on Wilson disease and Menkes disease in Leipzig/Germany(April16±18,2001) 2 .Afterthemeeting,apreliminarydraft ofaconsensusreportwasmailedtoallactiveparticipantsandtheir comments were incorporated in the ®nal text. Peter Ferenci 1 , Karel Caca 2 , Georgios Loudianos 3 , Georgina Mieli-Vergani 4 , Stuart Tanner 5 , Irmin Sternlieb 6 , Michael Schilsky 7 , Diane Cox 8 and Frieder Berr 2 1 Internal Medicine IV, Gastroenterology and Hepatology, University of Vienna, Austria, 2 Medizinische Klinik & Poliklinik II, Universita Ètsklinikum Leipzig, Germany, 3 Ospedale Regionale per Le Microcitemie, Cagliari, Italy, 4 Department of Child Health, King's College Hospital, London, UK, 5 University Division of Child Health, The Children'sHospital,Sheffield,UK, 6 TheNational Center for the Study of Wilson's Disease, New York,NY, 7 DivisionofLiverDiseases,Recanati/ Miller Transplant Institute, Mount Sinai Hospital, New York, NY, USA, and 8 Department of Medical Genetics, University of Alberta, Edmonton, Canada Peter Ferenci, MD, Prof. of medicine, Department of Internal Medicine IV, Gastroenterology and Hepatology, Wa Èhringer Gu Èrtel 18-20, A-1090 Wien, Austria. Tel:  431404004752. Fax:  431404004735. Received 23 December 2002, accepted 24 February 2003 Phenotypic classification Therewasgeneralagreementtoclassifysymptoma- ticpatientsaccordingtothemajororganinvolved intheirpresentingsymptoms(seeTable1). Diagnosis of Wilson disease in symptomatic patients There was general agreement that diagnosis of Wilsondiseaseshouldbebasedonacombination of clinical symptoms, laboratory test and the resultsofmutationanalysis(seeTable2). Patientspresentingwithneurologicalsymptoms(N1, N2,Nx) If in addition to the extrapyramidal symptoms, Kayser-Fleischer [KF] rings and typical labora- tory tests (ceruloplasmin below the lower limit of normal, high urinary copper excretion [>100 mg/d]) are present, diagnosis of Wilson dis- ease is straightforward (8). Further tests are not required. 1 Final report of the proceedings of the working party at the 8th International Meeting on Wilson disease and Menkes disease, Leipzig/Germany, April 16±18,2002. 2 ThismeetingwasorganizedundertheauspicesoftheEuropean Association for the Study of the Liver (EASL) and was ®nan- cially supported by the European Commission (High-level Scienti®c Conference No. HPCF-CT-2000-00327) and the AustrianSocietyofGastroenterologyandHepatology(O È GGH). 139 Liver International 2003: 23: 139±142 Printed in Denmark. All rights reserved Copyright ß Blackwell Munksgaard 2003 Liver International ISSN 1478-3223