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Title: Wilson disease: revision of diagnostic criteria in a clinical series with great genetic homogeneity
Authors: García-Villarreal, Luis
Hernández-Ortega, Andrea
Sánchez-Monteagudo, Ana
Peña Quintana, Luis 
Ramírez-Lorenzo, Teresa
Riaño, Marta
Moreno Pérez, Raquel Isabel 
Monescillo, Alberto
González-Santana, Daniel
Quiñones, Ildefonso
Sánchez-Villegas, Almudena 
Olmo-Quintana, Vicente
Garay Sanchez, Paloma 
Espinós, Carmen
González, Jesús M.
Tugores, Antonio 
UNESCO Clasification: 320506 Nefrología
320503 Gastroenterología
320607 Elementos minerales en la alimentación
320102 Genética clínica
Keywords: Ceruloplasmin
Wilson Disease
Issue Date: 2021
Journal: Journal of Gastroenterology 
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 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.
ISSN: 0944-1174
DOI: 10.1007/s00535-020-01745-0
Source: Journal of Gastroenterology [ISSN 0944-1174], v. 56, p. 78–89
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