{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T20:11:45Z","timestamp":1790194305612,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T00:00:00Z","timestamp":1743638400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Primary mitochondrial diseases are clinically heterogeneous and present diagnostic challenges due to the highly variable genotype\u2013phenotype correlation. Clinical symptoms can range from non\u2010specific fatigue, exercise intolerance, and weakness to syndromic phenotypes. Though multiple testing modalities exist to identify mitochondrial diseases, most of these tests are nonspecific, or results are associated with other diseases. Molecular testing can provide an efficient path toward diagnosis, as molecular detection techniques have improved and become less costly. A \u201cgenetics first\u201d approach can reduce diagnostic delay and improve management, where the diagnostic pathway can be an invasive or noninvasive combination of targeted or comprehensive molecular testing. Prior to ordering these tests, clinicians must consider the ambiguities and nuances of various testing modalities during the work\u2010up for mitochondrial diseases. Therefore, due to the diagnostic challenges associated with primary mitochondrial diseases, diagnosis should be made in the context of clinical and molecular data, potentially supplemented with histochemical and biochemical evidence. Confirmation of a diagnosis leads to improvements in the management of the disease, decreases unnecessary testing, informs reproductive planning, and improves research pipelines.<\/jats:p>","DOI":"10.1002\/mus.28387","type":"journal-article","created":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T22:40:47Z","timestamp":1743806447000},"page":"949-954","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Diagnosis of Primary Mitochondrial Diseases"],"prefix":"10.1002","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4702-9380","authenticated-orcid":false,"given":"Salman","family":"Bhai","sequence":"first","affiliation":[{"name":"Department of Neurology University of Texas Southwestern Medical Center  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michio","family":"Hirano","sequence":"additional","affiliation":[{"name":"H. Houston Merritt Center for Neuromuscular and Mitochondrial Disorders, Columbia Translational Neuroscience Initiative, Department of Neurology Columbia University Medical Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,3]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-019-0173-8"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2000.00057.x"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000230"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-022-04303-x"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-023-00783-1"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/13779"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genom-082509-141720"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1003"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0060204"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2012-303528"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-013-7225-3"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3966"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32703"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13201"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds435"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adi4038"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1086\/519394"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awp158"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2012.08.004"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.40.12.896"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24362"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24551"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.3233\/JND-140041"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/WNO.0000000000001984"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.3233\/JND-210786"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2014.177"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2012.03.017"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2007.11.018"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq310"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-15-91"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-020-04422-5"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51104"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm6070064"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2018.00400"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000200745"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-018-0022-1"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-019-1127-0"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awg028"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.24107"}],"container-title":["Muscle &amp; Nerve"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mus.28387","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T12:04:47Z","timestamp":1746705887000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mus.28387"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,3]]},"references-count":40,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1002\/mus.28387"],"URL":"https:\/\/doi.org\/10.1002\/mus.28387","archive":["Portico"],"relation":{},"ISSN":["0148-639X","1097-4598"],"issn-type":[{"value":"0148-639X","type":"print"},{"value":"1097-4598","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,3]]},"assertion":[{"value":"2024-06-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}