TY - JOUR A1 - Núñez Manchón, Judit AU - Ballester López, Alfonsina AU - Koehorst, Emma AU - Linares Pardo, Ian AU - Coenen, Daniëlle M. AU - Ara, Ignacio AU - Rodríguez López, Carlos AU - Ramos Fransi, Alba AU - Lucía Mulas, Alejandro AU - Nogales-Gadea, Gisela AU - Et al. T1 - Manifesting heterozygotes in McArdle disease: A myth or a reality—role of statins Y1 - 2018 SN - 0141-8955 UR - http://hdl.handle.net/11268/7354 AB - 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. © 2018 SSIEM KW - McArdle disease KW - Genética humana KW - Genética humana KW - Investigación médica LA - eng ER -