Identificador persistente para citar o vincular este elemento: http://hdl.handle.net/10553/75560
Título: Wilson disease: revision of diagnostic criteria in a clinical series with great genetic homogeneity
Autores/as: García-Villarreal, Luis
Hernández-Ortega, Andrea
Sánchez-Monteagudo, Ana
Peña Quintana, Luis 
Ramírez-Lorenzo, Teresa
Riaño, Marta
Moreno Pérez, Raquel Isabel 
Monescillo Francia, Alberto Fernando 
González-Santana, Daniel
Quiñones, Ildefonso
Sánchez-Villegas, Almudena 
Olmo-Quintana, Vicente
Garay Sanchez, Paloma 
Espinós, Carmen
González, Jesús M.
Tugores, Antonio 
Clasificación UNESCO: 320506 Nefrología
320503 Gastroenterología
320607 Elementos minerales en la alimentación
320102 Genética clínica
Palabras clave: Ceruloplasmin
Genetics
Wilson Disease
Fecha de publicación: 2021
Publicación seriada: Journal of Gastroenterology 
Resumen: Background: Wilson disease is an autosomal recessive disorder of copper metabolism caused by mutations in the ATP7B gene. An early diagnosis is crucial to prevent evolution of the disease, as implantation of early therapeutic measures fully prevents its symptoms. As population genetics data predict a higher than initially expected prevalence, it was important to define the basic diagnostic tools to approach population screening. Methods: A highly genetically homogeneous cohort of 70 patients, belonging to 50 unrelated families, has been selected as a framework to analyze all their clinical, biochemical and genetic characteristics, to define the disease in our population, with an estimated prevalence of 1 in 12,369, and determine the most useful features that reach diagnostic value. Results: Serum ceruloplasmin below 11.5 mg/dL and cupremia below 60 μg/mL, were the best analytical predictors of the disease in asymptomatic individuals, while cupruria or hepatic copper determination were less powerful. Genetic analysis reached a conclusive diagnosis in all 65 patients available for complete testing. Of them, 48 were carriers of at least one p.Leu708Pro mutant allele, with 24 homozygotes. Nine patients carried a promoter deletion mutation, revealing that extended sequencing beyond the ATP7B gene-coding region is essential. All mutations caused hepatic damage since early ages, increasing its severity as diagnosis was delayed, and neurological symptoms appear. Conclusion: Serum ceruloplasmin determination followed by genetic screening would reduce costs and favor the prioritization of non-invasive procedures to reach a definitive diagnosis, even for asymptomatic cases.
URI: http://hdl.handle.net/10553/75560
ISSN: 0944-1174
DOI: 10.1007/s00535-020-01745-0
Fuente: Journal of Gastroenterology [ISSN 0944-1174], v. 56 (1), p. 78–89, (2021)
Colección:Artículos
Vista completa

Google ScholarTM

Verifica

Altmetric


Comparte



Exporta metadatos



Los elementos en ULPGC accedaCRIS están protegidos por derechos de autor con todos los derechos reservados, a menos que se indique lo contrario.