Neurological manifestations and ATP7B mutations in Wilson's disease

Received 27 April 2007; received in revised form 23 July 2007; accepted 3 August 2007.

Abstract

Wilson's disease (WD) is a rare inborn metabolic error characterized by deficient biliary copper excretion secondary to ATP7B gene mutations. Neurological presentations are variable in respect to both pattern and age of onset; commonly a movement disorder presents in the second or third decade. The aim of this study was to ascertain genotype correlations with distinct neurological manifestations in 41 WD patients in a Brazilian center for WD. A total of 23 distinct mutations were detected, and the frameshift 3402delC had the highest allelic frequency (31.7%). An association between 3402delC and dysphagia was detected (p=0.01) but the limited number of patients is insufficient to allow one to draw conclusions. Both clinical studies analyzing larger cohorts and basic research on ATP7B protein function could potentially shed more light on our understanding of WD.

Keywords: ATP7B mutations, Genotype–phenotype correlations, Neurological manifestations, Wilson's disease

a Department of Neurology, University of São Paulo School of Medicine, São Paulo, Brazil

b Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil

c Medizinische Klinik m. S. Gastroenterologie, Hepatologie und Endokrinologie—Charité Campus Mitte, Berlin, Germany

d Transplantations Hepatologie, Universitätsklinikum, Münster, Germany

Corresponding author. R. Francisco Leitão, 479, ap 92, CEP 05414-020 São Paulo, SP, Brazil. Tel.: +551130635806; fax: +551130628666.

PII: S1353-8020(07)00171-X

doi:10.1016/j.parkreldis.2007.08.002

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