Manifesting heterozygotes in McArdle disease: a myth or a realityrole of statins

Judit Nunez-Manchon, Alfonsina Ballester-Lopez, Emma Koehorst, Ian Linares-Pardo, Danielle Coenen, Ignacio Ara, Carlos Rodriguez-Lopez, Alba Ramos-Fransi, Alicia Martinez-Pineiro, Giuseppe Lucente, Miriam Almendrote, Jaume Coll-Canti, Guillem Pintos-Morell, Alejandro Santos-Lozano, Joaquin Arenas, Miguel Angel Martin, Mauricio de Castro, Alejandro Lucia, Alfredo Santalla, Gisela Nogales-Gadea*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


McArdle disease is an autosomal recessive condition caused by deficiency of the PYGM gene-encoded muscle isoform of glycogen phosphorylase. Some cases of manifesting heterozygotes or carriers (i.e., patients who show some McArdle-like symptoms or signs despite being carriers of only one mutated PYGM 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 manifesting heterozygotes of McArdle disease and, if existing, whether statin treatment can trigger such condition. Eighty-one relatives of McArdle patients (among a total of 16 different families) were studied. We determined whether they were carriers of PYGM 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-carriers of PYGM mutations. Although we found existence of heterozygotes manifesting some exercise-related 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-intensity exercise, both of which are hallmarks of McArdle disease. On the other hand, statin myotoxicity was not associated with muscle symptom onset.

Original languageEnglish
Pages (from-to)1027-1035
Number of pages9
JournalJournal of Inherited Metabolic Disease
Issue number6
Publication statusPublished - Dec 2018


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