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Adenosine monophosphate-activated protein kinase disease mimicks hypertrophic cardiomyopathy and Wolff-Parkinson-White syndrome - Natural history

Murphy, RT; Mogensen, J; McGarry, K; Bahl, A; Evans, A; Osman, E; Syrris, P; ... McKenna, WJ; + view all (2005) Adenosine monophosphate-activated protein kinase disease mimicks hypertrophic cardiomyopathy and Wolff-Parkinson-White syndrome - Natural history. J AM COLL CARDIOL , 45 (6) 922 - 930. 10.1016/j.jacc.2004.11.053.

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Abstract

OBJECTIVES The aim of this study was to investigate the clinical expression of adenosine monophosphate-activated protein kinase (AMPK) gene mutations (PRKAG2) in adenosine monophosphate (AMP) kinase disease based on 12 years follow-up of known mutation carriers and to define the prevalence of PRKAG2 mutations in hypertrophic cardiomyopathy (HCM).BACKGROUND Adenosine monophosphate-activated protein kinase gene mutations cause HCM with Wolf-Parkinson-White syndrome and conduction disease.METHODS Clinical evaluation of 44 patients with known AMP kinase disease was analyzed. Mutation analysis of PRKAG2 was performed by fluorescent single-strand confirmation polymorphism analysis and direct sequencing of abnormal conformers in 200 patients with HCM.RESULTS Only one additional mutation was identified. The mean age at clinical diagnosis in the 45 gene carriers was 24 years (median 20 years, range 9 to 55 years). Symptoms of palpitation, dypspnea, chest pain, or syncope were present in 31 (69%) gene carriers; 7 (15%) complained of myalgia and had clinical evidence of proximal myopathy. Skeletal muscle biopsy showed excess mitochondria and ragged red fibers with minimal glycogen accumulation. Disease penetrance defined by typical electrocardiogram abnormalities was 100% by age 18 years. Thirty-two of 41 adults (78%) had left ventricular hypertrophy (LVH) on echocardiography, and progressive LVH was documented during follow-up. Survival was 91% at a mean follow-up of 12.2 years. Progressive conduction disease required pacemaker implantation in 17 of 45 (38%) at a mean age of 38 years.CONCLUSIONS The AMP kinase disease is uncommon in HCM and is characterized by progressive conduction disease and cardiac hypertrophy and includes extracardiac manifestations such as a skeletal myopathy, consistent with a systemic metabolic storage disease. Defects in adenosine triphosphate utilization or in specific cellular substrates, rather than mere passive deposition of amylopectin, may account for these clinical features. (c) 2005 by the American College of Cardiology Foundation.

Type: Article
Title: Adenosine monophosphate-activated protein kinase disease mimicks hypertrophic cardiomyopathy and Wolff-Parkinson-White syndrome - Natural history
DOI: 10.1016/j.jacc.2004.11.053
Keywords: LEFT-VENTRICULAR HYPERTROPHY, CARDIAC-HYPERTROPHY, GAMMA(2) SUBUNIT, MUTATIONS, SYSTEM, ONSET
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science > Clinical Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health
URI: http://discovery.ucl.ac.uk/id/eprint/119281
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