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Some cases of \u201cmanifesting\u201d heterozygotes or carriers (i.e., patients who show some McArdle\u2010like symptoms or signs despite being carriers of only one mutated <jats:italic>PYGM<\/jats:italic> allele) have been reported in the literature but there is controversy, with misdiagnosis being a possibility. The purpose of our study was to determine if there are actually \u201cmanifesting\u201d heterozygotes of McArdle disease and, if existing, whether statin treatment can trigger such condition. Eighty\u2010one relatives of McArdle patients (among a total of 16 different families) were studied. We determined whether they were carriers of <jats:italic>PYGM<\/jats:italic> mutations and also collected information on exercise tests (second wind and modified Wingate anaerobic test) and statin intake. We found 50 carriers and 31 non\u2010carriers of <jats:italic>PYGM<\/jats:italic> mutations. Although we found existence of heterozygotes manifesting some exercise\u2010related muscle problems such as exacerbated myalgia or weakness, they only accounted for 14% of the carriers and muscle symptoms were milder than those commonly reported in patients. Further, no carrier (whether reporting symptoms or not) showed the second wind phenomenon or a flat blood lactate response to maximal\u2010intensity exercise, both of which are hallmarks of McArdle disease. On the other hand, statin myotoxicity was not associated with muscle symptom onset.<\/jats:p>","DOI":"10.1007\/s10545-018-0203-2","type":"journal-article","created":{"date-parts":[[2018,6,20]],"date-time":"2018-06-20T09:55:51Z","timestamp":1529488551000},"page":"1027-1035","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Manifesting heterozygotes in McArdle disease: a myth or a reality\u2014role of statins"],"prefix":"10.1002","volume":"41","author":[{"given":"Judit","family":"N\u00fa\u00f1ez\u2010Manch\u00f3n","sequence":"first","affiliation":[{"name":"Grup de Recerca en Malalties Neuromusculars i Neuropediatriques Institut d'Investigaci\u00f3 en Ci\u00e8ncies de la Salut Germans Trias i Pujol, Campus Can Ruti, Universitat Aut\u00f2noma de Barcelona Badalona Barcelona 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January 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 May 2018","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 May 2018","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 June 2018","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 July 2018","order":5,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":6,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Unfortunately the name of one of the authors was spelled incorrectly in the published original article. The correct name is Alejandro Santos-Lozano. The original article got updated.","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"Judit N\u00fa\u00f1ez-Manch\u00f3n declares that she is supported by a contract in the project AFM Telethon #21108. Alfonsina Ballester-Lopez declares funding by an FI Agaur fellowship FI_B 01090. Emma Koehorst declares that she is supported by a contract in the project PI15\/01756 from Instituto de Salud Carlos III cofinanced by FEDER. Ian Linares-Pardo declares that he has a contract in the Miguel Servet project CP14\/00032 cofinanced by FEDER. Dani\u00eblle Coenen, Ignacio Ara, Alba Ramos-Fransi, Alicia Martinez Pi\u00f1eiro, Miriam Almendrote, Jaume Coll, Alejandro Santos Lozano, Mauricio de Castro, and Alfredo Santalla declare that they have no conflict of interest. Carlos Rodriguez-Lopez declares funding by Secretar\u00eda de Estado de Investigaci\u00f3n, Desarrollo e Innovaci\u00f3n fellowship BES-2016-077199. Giuseppe Lucente declares that he is supported by a Rio Hortega contract (ISCIII CM16\/00016 and FEDER). Guillem Pintos-Morell declares that he had had personal fees from Shire, and from BioMarin, outside the submitted work. Joaquin Arenas declares that he has a grant of the Instituto de Salud Carlos III and FEDER. Miguel Angel Mart\u00edn declares that he has a grant of the Instituto de Salud Carlos III and FEDER. Alejandro Lucia declares that he has a grant of the Instituto de Salud Carlos III and FEDER. Gisela Nogales-Gadea declares grants from, Madrid, Spain (CP14\/00032, PI15\/01756 and FEDER) and France, AMF Telethon Trampoline Grant No. 21108.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All procedures followed were in accordance with the ethical standards of the responsible committee of the University Hospital Germans Trias i Pujol (study reviewed and approved by this committee with ref. PI-18-027) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"value":"This article does not contain any studies with animal subjects performed by the any of the authors.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Animal rights"}}]}}