Neurological manifestations and ATP7B mutations in Wilson's disease

Machado, Alexandre Aluizio Costa; Deguti, Marta Mitiko; Genschel, Janine; Cançado, Eduardo Luiz Rachid; Bochow, Bettina; Schmidt, Hartmut; Barbosa, Egberto Reis

doi:10.1016/j.parkreldis.2007.08.002

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Volume 14, Issue 3 , Pages 246-249, April 2008

Neurological manifestations and ATP7B mutations in Wilson's disease

Alexandre Aluizio Costa Machado
- Department of Neurology, University of São Paulo School of Medicine, São Paulo, Brazil
- Corresponding author. R. Francisco Leitão, 479, ap 92, CEP 05414-020 São Paulo, SP, Brazil. Tel.: +551130635806; fax: +551130628666.
Marta Mitiko Deguti
- Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil
Janine Genschel
- Medizinische Klinik m. S. Gastroenterologie, Hepatologie und Endokrinologie—Charité Campus Mitte, Berlin, Germany
Eduardo Luiz Rachid Cançado
- Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil
Bettina Bochow
- Medizinische Klinik m. S. Gastroenterologie, Hepatologie und Endokrinologie—Charité Campus Mitte, Berlin, Germany
Hartmut Schmidt
- Medizinische Klinik m. S. Gastroenterologie, Hepatologie und Endokrinologie—Charité Campus Mitte, Berlin, Germany
- Transplantations Hepatologie, Universitätsklinikum, Münster, Germany
Egberto Reis Barbosa
- Department of Neurology, University of São Paulo School of Medicine, São Paulo, Brazil

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