{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T04:11:12Z","timestamp":1788667872235,"version":"build-2803163510"},"reference-count":28,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100011110","name":"UCB","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011110","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Therapeutic Advances in Rare Disease"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:p>The inaugural United Mitochondrial Disease Foundation (UMDF) Mitochondrial Medicine 2025 Masterclass focused on primary mitochondrial diseases (PMDs) especially primary mitochondrial myopathies (PMMs) and thymidine kinase 2 deficiency (TK2d). The Masterclass featured leading US experts in the field, providing the latest scientific and clinical knowledge, as well as patients and caregivers sharing their lived experience of mitochondrial diseases. In this report, we summarize the key highlights of each presentation. An overview of PMM featuring the etiologies of different PMMs and key features of notable PMMs, was followed by a presentation discussing the practical clinical processes of diagnosing PMM, how the roles of clinicians have evolved as diagnostic technology has improved, and actions clinicians can take to maximize the chances of an early, accurate diagnosis. Real-world case studies highlighted variations in disease presentation among the wide range of PMMs, which was followed by an in-depth review of clinical assessments and symptom management for PMM across organ systems. Multisystemic disorders like PMM require multidisciplinary management, in both a chronic and acute setting, and two experts discussed the practical workflow for clinicians to build a multidisciplinary model of care at their hospitals, the roles and responsibilities of the lead coordinator and each subspecialist, and practical steps that clinicians can take to manage acute care coordination and decrease acute care utilization. A hypothetical case study of TK2d (based on real patients) brought together the different aspects of PMM discussed during the Masterclass, while the patient perspective presentations allowed patients and caregivers to discuss the real-world impact that the diagnostic and care journey had on them and their families. This Educational Masterclass provided detailed knowledge of PMM designed to provide the next generation of clinicians and investigators with practical, actionable guidance and resources they could utilize to make a difference in the lives of patients with PMM.<\/jats:p>","DOI":"10.1177\/26330040261478640","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T13:59:49Z","timestamp":1788443989000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Progress and perspectives in primary mitochondrial myopathy: Highlights from the 2025 mitochondrial medicine masterclass with a focus on TK2 deficiency"],"prefix":"10.1177","volume":"7","author":[{"given":"Austin","family":"Larson","sequence":"first","affiliation":[{"name":"Pediatrics-Clinical Genetics and Metabolism Department, University of Colorado Anschutz Medical Campus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared","family":"Goettemoeller","sequence":"additional","affiliation":[{"name":"United Mitochondrial Disease Foundation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Goettemoeller","sequence":"additional","affiliation":[{"name":"United Mitochondrial Disease Foundation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Goettemoeller","sequence":"additional","affiliation":[{"name":"United Mitochondrial Disease Foundation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Goldstein","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Philadelphia"},{"name":"University of Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikki","family":"Huggan","sequence":"additional","affiliation":[{"name":"United Mitochondrial Disease Foundation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5781-9824","authenticated-orcid":false,"given":"Amel","family":"Karaa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Leahey","sequence":"additional","affiliation":[{"name":"United Mitochondrial Disease Foundation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Scaglia","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine and Texas Children\u2019s Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Yeske","sequence":"additional","affiliation":[{"name":"United Mitochondrial Disease Foundation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0743-8879","authenticated-orcid":false,"given":"Zarazuela","family":"Zolkipli-Cunningham","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Philadelphia"},{"name":"University of Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michio","family":"Hirano","sequence":"additional","affiliation":[{"name":"Columbia University Irving Medical Center"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1177\/21501319231193875"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0197513"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.3109\/07853890.2011.605389"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/crt2.41"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1212\/CPJ.0000000000200229"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000743"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000219759.72195.41"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl282"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2012.10.005"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn252"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1177\/0883073814538512"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.6.1047"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2016.04.009"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2017.107"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2010.02062.x"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000209779"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2008-0205"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2017.04.007"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1097\/MLR.0000000000001388"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-018-0949-5"},{"key":"e_1_3_5_22_2","doi-asserted-by":"crossref","unstructured":"Ma Y Hines L Agne M et al. Prevalence estimation of thymidine kinase 2 deficiency an ultra-rare autosomal recessive mitochondrial disease. In: Poster presented at: ISPOR Europe 2023 Copenhagen Denmark 12\u201315 November 2023.","DOI":"10.1016\/j.jval.2023.09.1182"},{"key":"e_1_3_5_23_2","volume-title":"StatPearls","author":"Hameed S","year":"2025","unstructured":"Hameed S, Tadi P. Myoclonic epilepsy and ragged red fibers. StatPearls [Internet]. StatPearls Publishing, 2025."},{"key":"e_1_3_5_24_2","volume-title":"MedlinePlus. Kearns-Sayre syndrome","author":"National Library of Medicine","year":"2011","unstructured":"National Library of Medicine. MedlinePlus. Kearns-Sayre syndrome. The Library. https:\/\/medlineplus.gov\/genetics\/condition\/kearns-sayre-syndrome\/#frequency (2011, accessed 7 November 2025)."},{"key":"e_1_3_5_25_2","volume-title":"MELAS","author":"United Mitochondrial Disease Foundation","year":"2025","unstructured":"United Mitochondrial Disease Foundation. MELAS. The Foundation. https:\/\/umdf.org\/melas\/ (2025, accessed 7 November 2025)."},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-021-02319-4"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.3233\/JND-140045"},{"key":"e_1_3_5_28_2","volume-title":"Newborn screening for Pompe disease: a summary of the evidence and advisory committee decision","author":"Health and Resources and Services Administration","year":"2013","unstructured":"Health and Resources and Services Administration. Newborn screening for Pompe disease: a summary of the evidence and advisory committee decision. Health and Resources and Services Administration. https:\/\/www.hrsa.gov\/sites\/default\/files\/hrsa\/advisory-committees\/heritable-disorders\/pompe-27-june-2018.pdf (2013, accessed 7 November 2025)."},{"key":"e_1_3_5_29_2","volume-title":"MedlinePlus. Leigh syndrome","author":"National Library of Medicine","year":"2023","unstructured":"National Library of Medicine. MedlinePlus. Leigh syndrome. The Library. https:\/\/medlineplus.gov\/genetics\/condition\/leigh-syndrome\/#frequency (2023, accessed 7 November 2025)."}],"container-title":["Therapeutic Advances in Rare Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/26330040261478640","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/26330040261478640","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/26330040261478640","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T03:42:05Z","timestamp":1788666125000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/26330040261478640"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":28,"alternative-id":["10.1177\/26330040261478640"],"URL":"https:\/\/doi.org\/10.1177\/26330040261478640","relation":{},"ISSN":["2633-0040","2633-0040"],"issn-type":[{"value":"2633-0040","type":"print"},{"value":"2633-0040","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]},"article-number":"26330040261478640"}}