Wilson disease: revision of diagnostic criteria in a clinical series with great genetic homogeneity
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ORIGINAL ARTICLE—LIVER, PANCREAS, AND BILIARY TRACT
Wilson disease: revision of diagnostic criteria in a clinical series with great genetic homogeneity Luis Garcı´a-Villarreal1 • Andrea Herna´ndez-Ortega2 • Ana Sa´nchez-Monteagudo3 Luis Pen˜a-Quintana2,4 • Teresa Ramı´rez-Lorenzo1 • Marta Rian˜o5 • Raquel Moreno-Pe´rez6 • Alberto Monescillo7 • Daniel Gonza´lez-Santana2 • Ildefonso Quin˜ones8 • Almudena Sa´nchez-Villegas9 • Vicente Olmo-Quintana10 • Paloma Garay-Sa´nchez1 • Carmen Espino´s3 • Jesu´s M. Gonza´lez1 • Antonio Tugores1
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Received: 19 May 2020 / Accepted: 24 October 2020 Ó Japanese Society of Gastroenterology 2020
Abstract 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
Luis Garcı´a-Villarreal and Andrea Herna´ndez-Ortega contributed equally to this work and should be both considered as co-first authors.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00535-020-01745-0) contains supplementary material, which is available to authorized users.
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 lg/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,
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Department of Clinical Biochemistry and Clinical Analyses, Complejo Hospitalario Universitario Insular MaternoInfantil, Las Palmas de Gran Canaria, Spain
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Department of Nursery. Atencion Primaria, Las Palmas de Gran Canaria, Spain
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Department of Gastroenterology, Complejo Hospitalario Universitario Insular Materno-Infantil, Las Palmas de Gran Canaria, Spain
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Department of Gastroenterology. Hospital, Universitario Dr Negrı´n, Las Palmas de Gran Canaria, Spain
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Department of Public Health, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain
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Department of Pharmacy, Atencion Primaria, Las Palmas de Gran Canaria, Spain
& Antonio Tugores [email protected]
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