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Manifestations and Evolution of Wilson Disease in Pediatric Patients Carrying ATP7B Mutation L708P

Peña-Quintana, Luis*; García-Luzardo, María R.; García-Villarreal, Luis; Arias-Santos, María D.§; Garay-Sánchez, Paloma; Santana, Alfredo||; González-Santana, Daniel; Ramos-Varela, Juan C.; Rial-González, Ramiro; Tugores, Antonio

Journal of Pediatric Gastroenterology & Nutrition: January 2012 - Volume 54 - Issue 1 - p 48–54
doi: 10.1097/MPG.0b013e318230130c
Original Articles: Hepatology and Nutrition

Objectives: The aim of the study was to characterize a group of 11 pediatric patients, ages 3 to 13 years, affected by Wilson disease (WD) in the island of Gran Canaria, Spain.

Patients and Methods: Genetic, biochemical, and pathological features, together with their response to treatment and clinical evolution, have been analyzed for this group of patients.

Results: Genetically, the group was rather homogeneous, with an extremely high prevalence of the L708P mutation (4 homozygotes and 5 heterozygotes). Despite being initially screened because of asymptomatic hypertransaminemia, all of the patients presented with some degree of liver damage that was never accompanied by any neurological manifestation. Hepatic damage was most severe in a compound heterozygote with a novel mutation, G1266W, affecting a motif in the ATP7B polypeptide that is greatly conserved in similar proteins among metazoans. Ceruloplasmin and copper serum levels, together with the determination of hepatic copper content, were found to be of great diagnostic value, whereas urine copper measurements were found to be much less conclusive. All of the patients responded well to treatment with D-penicillamine with no documented adverse reactions.

Conclusions: The patients in Gran Canaria constitute, overall, one of the largest groups of patients with WD with a high incidence of a single mutation, allowing us to define the early clinical symptoms and the evolution of the disease in patients carrying the ATP7B L708P mutant allele, and the study of WD in a genetically homogeneous background.

*Departamento de Ciencias Clínicas, Universidad de Las Palmas de Gran Canaria

Unit of Pediatric Gastroenterology, Hepatology and Nutrition

Unit of Research

§Department of Pathology

||Unit of Genetics, Complejo Hospitalario Universitario Insular Materno-Infantil, Las Palmas de Gran Canaria, Spain.

Address correspondence and reprint requests to Antonio Tugores, Unit of Research, Unidad de Investigación, Complejo Hospitalario Universitario Insular Materno-Infantil, Avenida Maritima del Sur s/n, Las Palmas de Gran Canaria 35016, Spain (e-mail: atugores@yahoo.com).

Received 28 March, 2011

Accepted 15 June, 2011

This work was supported by the Servicio Canario de Salud. Parts of the infrastructures used were provided by grants IF05/3705, IF06/3632, IF07/3616, and IF08/3620 from the Instituto de Salud Carlos III/FIS.

The authors report no conflicts of interest.

Copyright 2012 by ESPGHAN and NASPGHAN