{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T18:15:09Z","timestamp":1761848109699,"version":"build-2065373602"},"reference-count":22,"publisher":"Walter de Gruyter GmbH","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_jpem-2024-0622_abs_001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>McArdle disease (also known as glycogen storage disease type V) is a rare metabolic myopathy that is caused by myophosphorylase deficiency, leading to impaired glycogenolysis in skeletal muscles. This study explored the clinical, histopathological, and genetic landscape of McArdle disease in a regional cohort from Turkey, emphasizing diagnostic and management challenges.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jpem-2024-0622_abs_102\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A retrospective analysis was conducted on 350 muscle biopsies performed between 2013 and 2024 in a tertiary care center.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jpem-2024-0622_abs_202\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Seven patients (2.1\u202f%) were diagnosed with McArdle disease. The clinical features included exercise intolerance (100\u202f%), muscle pain (75\u202f%), and the second wind phenomenon (62.5\u202f%). Two patients presented with acute renal failure due to rhabdomyolysis with myoglobinuria, leading to metabolic acidosis. Histopathological findings revealed glycogen accumulation in subsarcolemmal vacuoles and absent myophosphorylase activity in all cases. Genetic analysis identified five distinct\n                      <jats:italic>PYGM<\/jats:italic>\n                      pathogenic variants, including c.808C&gt;T (p.Arg270Ter) and c.2262del (p.Lys754fs). These findings highlight the phenotypic and genetic heterogeneity of McArdle disease.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_jpem-2024-0622_abs_003\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>McArdle disease remains underdiagnosed due to its variable clinical presentation and limited access to advanced diagnostic tools. This study underscores the importance of a multidisciplinary approach that integrates clinical assessment, muscle biopsy, and molecular analysis. Increased awareness and training among healthcare providers are critical for early recognition and intervention. Future research should focus on expanding genetic databases and exploring targeted therapies to improve outcomes in this challenging condition.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/jpem-2024-0622","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T12:03:47Z","timestamp":1758110627000},"page":"1187-1194","source":"Crossref","is-referenced-by-count":0,"title":["A disease that is difficult to predict: regional distribution and phenotypic, histopathological and genetic findings in McArdle disease"],"prefix":"10.1515","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9884-1112","authenticated-orcid":false,"given":"Bahattin","family":"Erdo\u011fan","sequence":"first","affiliation":[{"name":"Department of Pathology , Eskisehir City Hospital , Eskisehir , T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gonca K\u0131l\u0131\u00e7","family":"Y\u0131ld\u0131r\u0131m","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nutrition and Metabolism, Faculty of Medicine , Eskisehir Osmangazi University , Eskisehir , T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ezgi","family":"Susam","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics , Sakarya Training and Research Hospital , Sakarya , T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aziz Serhat","family":"Baykara","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery , Eskisehir City Hospital , Eskisehir , T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2025,9,9]]},"reference":[{"key":"2025103018011136394_j_jpem-2024-0622_ref_001","unstructured":"McArdle, B. Myopathy due to a defect in muscle glycogen breakdown. Clin Sci 1951;10:13\u201335."},{"key":"2025103018011136394_j_jpem-2024-0622_ref_002","unstructured":"Dubowitz, V, Caroline, AS, Anders, O. Muscle biopsy: a practical approach, 4th ed. London: Saunders; 2013:483 p."},{"key":"2025103018011136394_j_jpem-2024-0622_ref_003","doi-asserted-by":"crossref","unstructured":"Canda, E, K\u00f6se, M, Diniz, G. Metabolic and mitochondrial myopathies: clues for differential diagnosis of neuromuscular disorders. New York: Springer International Publishing; 2023:249 p.","DOI":"10.1007\/978-3-031-33924-0_14"},{"key":"2025103018011136394_j_jpem-2024-0622_ref_004","doi-asserted-by":"crossref","unstructured":"Vissing, J. Disorders of muscle glycogen metabolism. In: Goebel, HH, Caroline, AS, Weller, RO, editors. Muscle disease: pathology and genetics, 2nd ed. Oxford: Wiley Blackwell; 2013:254 p.","DOI":"10.1002\/9781118635469.ch28"},{"key":"2025103018011136394_j_jpem-2024-0622_ref_005","unstructured":"Biller, J, editor. The interface of neurology & internal medicine. Philadelphia: Lippincott Williams & Wilkins; 2008."},{"key":"2025103018011136394_j_jpem-2024-0622_ref_006","doi-asserted-by":"crossref","unstructured":"L\u00f8kken, N, Hansen, KK, Storgaard, JH, \u00d8rngreen, MC, Quinlivan, R, Vissing, J. Titrating a modified ketogenic diet for patients with McArdle disease: a pilot study. J\u00a0Inherit Metab Dis 2020;43:778\u201386. https:\/\/doi.org\/10.1002\/jimd.12223.","DOI":"10.1002\/jimd.12223"},{"key":"2025103018011136394_j_jpem-2024-0622_ref_007","doi-asserted-by":"crossref","unstructured":"Erdo\u011fan, B, Yimenicio\u011flu, S, Yarar, C, \u00d6zer, E, \u00c7arman, KB. Diagnostic effectiveness of muscle biopsy in neuromuscular diseases; four years of retrospective critical review. Tepecik E\u011fit ve Ara\u015ft Hast Derg 2019;29:46\u201337.","DOI":"10.5222\/terh.2019.99267"},{"key":"2025103018011136394_j_jpem-2024-0622_ref_008","unstructured":"IBM Corp. IBM SPSS Statistics for windows, version 28.0. Armonk, NY: IBM Corp; 2021."},{"key":"2025103018011136394_j_jpem-2024-0622_ref_009","doi-asserted-by":"crossref","unstructured":"Pushpa, RJ, Marcus, D, Stephan, Z. McArdle disease: clinical, biochemical, histological and molecular genetic analysis of 60 patients. Biomedicines 2020;8:33\u20138. https:\/\/doi.org\/10.3390\/biomedicines8020033.","DOI":"10.3390\/biomedicines8020033"},{"key":"2025103018011136394_j_jpem-2024-0622_ref_010","doi-asserted-by":"crossref","unstructured":"De Castro, M, Johnston, J, Biesecker, L. Determining the prevalence of McArdle disease from gene frequency by analysis of next-generation sequencing data. Genet Med 2015;17:1002\u20136. https:\/\/doi.org\/10.1038\/gim.2015.9.","DOI":"10.1038\/gim.2015.9"},{"key":"2025103018011136394_j_jpem-2024-0622_ref_011","doi-asserted-by":"crossref","unstructured":"Santalla, A, Nogales-Gadea, G, Encinar, AB, Vieitez, I, Gonz\u00e1lez-Quintana, A, Serrano-Lorenzo, P, et al.. Genotypic and phenotypic features of all Spanish patients with McArdle disease: a 2016 update. BMC Genom 2017;18:819. https:\/\/doi.org\/10.1186\/s12864-017-4188-2.","DOI":"10.1186\/s12864-017-4188-2"},{"key":"2025103018011136394_j_jpem-2024-0622_ref_012","doi-asserted-by":"crossref","unstructured":"Carvalho, AAS, Christofolini, DM, Perez, MM, Dutra, EH, Alonso, I, Oliveira, ASB, et al.. PYGM mRNA expression in McArdle disease: demographic, clinical, morphological and genetic features. PLoS One 2020;15:e0236597. https:\/\/doi.org\/10.1371\/journal.pone.0236597.","DOI":"10.1371\/journal.pone.0236597"},{"key":"2025103018011136394_j_jpem-2024-0622_ref_013","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Consuegra, I, Asensio-Pe\u00f1a, S, Garrido-Moraga, R, Pin\u00f3s, T, Dom\u00ednguez-Gonz\u00e1lez, C, Santalla, A, et al.. Identification of potential muscle biomarkers in McArdle disease: insights from muscle proteome analysis. Int J Mol Sci 2022;23:4650. https:\/\/doi.org\/10.3390\/ijms23094650.","DOI":"10.3390\/ijms23094650"},{"key":"2025103018011136394_j_jpem-2024-0622_ref_014","doi-asserted-by":"crossref","unstructured":"Llavero, F, Arrazola Sastre, A, Luque Montoro, M, G\u00e1lvez, P, Lacerda, HM, Parada, LA, et al.. McArdle disease: new insights into its underlying molecular mechanisms. Int J Mol Sci 2019;20:5919. https:\/\/doi.org\/10.3390\/ijms20235919.","DOI":"10.3390\/ijms20235919"},{"key":"2025103018011136394_j_jpem-2024-0622_ref_015","doi-asserted-by":"crossref","unstructured":"Vidal-Sanahuja, R, Ortez-Gonz\u00e1lez, CI, Nascimento-Osorio, A, Colomer-Oferil, J. McArdle\u2019s disease in four pediatric patients. Diagnostic algorithm for exercise intolerance. Rev Neurol 2022;75:129\u201336.","DOI":"10.33588\/rn.7506.2022212"},{"key":"2025103018011136394_j_jpem-2024-0622_ref_016","doi-asserted-by":"crossref","unstructured":"Pin\u00f3s, T, Andreu, AL, Bruno, C, Hadjigeorgiou, GM, Haller, RG, Lafor\u00eat, P, et al.. Creation and implementation of a European registry for patients with McArdle disease and other muscle glycogenoses. Orphanet J Rare Dis 2020;15:187. https:\/\/doi.org\/10.1186\/s13023-020-01455-z.","DOI":"10.1186\/s13023-020-01455-z"},{"key":"2025103018011136394_j_jpem-2024-0622_ref_017","doi-asserted-by":"crossref","unstructured":"Rawson, ES, Clarkson, PM, Tarnopolsky, MA. Perspectives on exertional rhabdomyolysis. Sports Med 2017;47:33\u201349. https:\/\/doi.org\/10.1007\/s40279-017-0689-z.","DOI":"10.1007\/s40279-017-0689-z"},{"key":"2025103018011136394_j_jpem-2024-0622_ref_018","doi-asserted-by":"crossref","unstructured":"Hamadeh, M, Nasrallah, K, Ajami, Z, Zeaiter, R, Abbas, L, Hamadeh, S, et al.. Clinical presentation and management of severe acute renal failure in McArdle disease. Clin Med Res 2021;19:90\u20133. https:\/\/doi.org\/10.3121\/cmr.2021.1641.","DOI":"10.3121\/cmr.2021.1641"},{"key":"2025103018011136394_j_jpem-2024-0622_ref_019","doi-asserted-by":"crossref","unstructured":"Migocka-Patrza\u0142ek, M, Elias, M. Muscle glycogen phosphorylase and its functional partners in health and disease. Cells 2021;10:883. https:\/\/doi.org\/10.3390\/cells10040883.","DOI":"10.3390\/cells10040883"},{"key":"2025103018011136394_j_jpem-2024-0622_ref_020","doi-asserted-by":"crossref","unstructured":"Kang, JH, Park, JH, Park, JS, Lee, SK, Lee, S, Baik, HW. Molecular diagnosis of McArdle disease using whole-exome sequencing. Exp Ther Med 2021;22:1029. https:\/\/doi.org\/10.3892\/etm.2021.10461.","DOI":"10.3892\/etm.2021.10461"},{"key":"2025103018011136394_j_jpem-2024-0622_ref_021","doi-asserted-by":"crossref","unstructured":"Taylor, RL, Davis, M, Turner, E, Brull, A, Pinos, T, Cabrera, M, et al.. Clinical utility gene card for McArdle disease. Eur J Hum Genet 2018;26:758\u201364. https:\/\/doi.org\/10.1038\/s41431-017-0070-6.","DOI":"10.1038\/s41431-017-0070-6"},{"key":"2025103018011136394_j_jpem-2024-0622_ref_022","doi-asserted-by":"crossref","unstructured":"Inal-G\u00fcltekin, G, Topta\u015f-Hekimo\u011flu, B, G\u00f6rmez, Z, Geli\u015fin, \u00d6, Durmu\u015f, H, Erg\u00fcner, B, et al.. Myophosphorylase (PYGM) mutations determined by next generation sequencing in a cohort from Turkey with McArdle disease. Neuromuscul Disord 2017;27:997\u20131008. https:\/\/doi.org\/10.1016\/j.nmd.2017.06.004.","DOI":"10.1016\/j.nmd.2017.06.004"}],"container-title":["Journal of Pediatric Endocrinology and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/jpem-2024-0622\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/jpem-2024-0622\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T18:01:47Z","timestamp":1761847307000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/jpem-2024-0622\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,9]]},"references-count":22,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,7,21]]},"published-print":{"date-parts":[[2025,11,25]]}},"alternative-id":["10.1515\/jpem-2024-0622"],"URL":"https:\/\/doi.org\/10.1515\/jpem-2024-0622","relation":{},"ISSN":["0334-018X","2191-0251"],"issn-type":[{"type":"print","value":"0334-018X"},{"type":"electronic","value":"2191-0251"}],"subject":[],"published":{"date-parts":[[2025,9,9]]}}}