Author information
1Universidad Las Palmas Gran Canaria. Servicio Digestivo, Complejo Hospitalario Universitario Insular Materno Infantil (CHUIMI), Las Palmas de Gran Canaria, Spain. Electronic address: pabloalonsoc1997@gmail.com.
2Unidad Apoyo Investigación, CHUIMI, Las Palmas de Gran Canaria, Spain. Electronic address: atugores@yahoo.com.
3LiverUnit, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain. Electronic address: zmarino@clinic.cat.
4Servicio Digestivo, Hospital Universitario La Paz, Madrid, Spain. Electronic address: aolveiram@gmail.com.
5Hospital Universitari i Politècnic La Fe, IISLaFe, Universidad de Valencia y Ciberehd, Valencia, Spain. Electronic address: marina.berenguer@uv.es.
6Complejo Hospitalario de Navarra, Pamplona, Spain. Electronic address: phuartem@navarra.es.
7Hospital Universitario de Cruces, Baracaldo, Spain. Electronic address: joseramon.fernandezramos@osakidetza.eus.
8Hospital Universitario Miguel Servet, Zaragoza, Spain. Electronic address: marialazarorios@hotmail.com.
9Hospital Universitario Central de Asturias, Oviedo, Spain. Electronic address: luisagondi@hotmail.com.
10Servicio de Aparato Digestivo, Complejo Hospitalario Universitario de Albacete, Facultad de Medicina Universidad de Castilla La Mancha, Spain. Electronic address: josemariamoren@yahoo.es.
11Hospital Universitario de Canarias, Santa Cruz Tenerife, Spain. Electronic address: mhernand@ull.edu.es.
12Hospital Universitario Virgen Macarena, Sevilla, Spain. Electronic address: paulafer7@gmail.com.
13Hospital Universitario A Coruña, A Coruña, Spain. Electronic address: manuel.delgado.blanco@sergas.es.
14Unidad de Hepatología, Unidad de Gestión Clínica de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga-Plataforma Bionand, Málaga, Spain. Electronic address: Josepinazo@hotmail.es.
15Hospital Universitario de Toledo, Toledo, Spain. Electronic address: m.romero.gutierrez@gmail.com.
16Hospital Universitario Virgen del Rocío, Sevilla, Spain. Electronic address: jampuero-ibis@us.es.
17Hospital UniversitariGermansTrias i Pujol, Badalona, Spain. Electronic address: hmasnou.germanstrias@gencat.cat.
18Hospital Universitario de Bellvitge, Hospitalet de Llobregat, Spain. Electronic address: alba.cachero@bellvitgehospital.cat.
19LiverUnit, Hospital Vall d'Hebron, Universitat Autónoma Barcelona, CIBERehd, Barcelona, Spain. Electronic address: victor.vargas@uab.cat.
20Hospital Universitario de Burgos, Burgos, Spain. Electronic address: jgomcam@hotmail.com.
21Hospital Universitario Virgen de la Luz, Cuenca, Spain. Electronic address: Julmorar@hotmail.com.
22Hospital Clínico de Santiago, Santiago de Compostela, Spain. Electronic address: esther.molina.perez@sergas.es.
23LiverUnit, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain. Electronic address: amiralpeix@recerca.clinic.cat.
24Grupo de Investigación Patología Médica, Instituto de Investigaciones Biomédicas y Sanitarias. Universidad de Las Palmas de Gran Canaria. Servicio Digestivo, Complejo Hospitalario Universitario Insular Materno Infantil (CHUIMI), Las Palmas de Gran Canaria, Spain. Electronic address: lgarciavillarreal@gmail.com.
Abstract
Background & aims: Wilson disease (WD) is a copper metabolism disorder caused by mutations in ATP7B gene, with significant clinical variability. Several studies have analyzed the prevalence and penetrance of mutations. We evaluated both characteristics for our more frequent mutations.
Methods: Evaluation of 260 patients from the National Registry: clinical, analytical and genetic data. Estimation of homozygotes and total cases according to Hardy-Weinberg equilibrium and comparison with Registry records.
Results: The estimated number of homozygotes were higher than registered: p.Met645Arg (1949/6), p.His1069Gln (20/8), p.Leu708Pro (63/24) and p.Gly869Arg (147/0). p.Met645Arg homozygotes presented less cirrhosis at diagnosis, extrahepatic disease and Kayser-Fleischer ring (KFR) and more presymptomatic cases and diagnosis after 40 years of age than p.Leu708Pro and p.His1069Gln homozygotes. p.Met645Arg homozygotes presented more late diagnosis than p.Met645Arg compound heterozygotes. Compound heterozygotes carrying p.Met645Arg or p.Gly869Arg showed less cirrhosis at diagnosis, KFR and neurological symptoms and more hepatic and presymptomatic cases, despite clearly low ceruloplasmin levels. The estimated prevalence was 1:3.785, predicting more than 10.500 patients.
Conclusions: The widespread mutations p.Met645Arg and p.Gly869Arg show low penetrance. WD might be underdiagnosed in Spain due to less severe phenotype of the most frequent mutations, a crucial fact to avoid misdiagnosis and to offer early therapy.