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We sought to characterize glucose and fat metabolism during rest, submaximal exercise, and postexercise rest in children, adolescents, and young adults with BTHS and unaffected controls and examine their relationships with cardioskeletal energetics and function. Children\/adolescents and young adults with BTHS (n\u2009=\u200929) and children\/adolescent and young adult control participants (n\u2009=\u200928, total n\u2009=\u200957) underwent an infusion of 6\u20326\u2032H2 glucose and U\u2010<jats:sup>13<\/jats:sup>C palmitate and indirect calorimetry during rest, 30\u2010minutes of moderate exercise (50% <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/jimd12094-math-0001.png\" xlink:title=\"urn:x-wiley:01418955:media:jimd12094:jimd12094-math-0001\"\/>), and recovery. Cardiac function, cardioskeletal mitochondrial energetics, and exercise capacity were examined via echocardiography, <jats:sup>31<\/jats:sup>P magnetic resonance spectroscopy, and peak exercise testing, respectively. The glucose turnover rate was significantly higher in individuals with BTHS during rest (33.2\u2009\u00b1\u20099.8 vs 27.2\u2009\u00b1\u20098.1 \u03bcmol\/kgFFM\/min, <jats:italic>P<\/jats:italic>\u2009&lt;\u2009.01) and exercise (34.7\u2009\u00b1\u200911.2 vs 29.5\u2009\u00b1\u20098.8 \u03bcmol\/kgFFM\/min, <jats:italic>P<\/jats:italic>\u2009&lt;\u2009.05) and tended to be higher postexercise (33.7\u2009\u00b1\u200910.2 vs 28.8\u2009\u00b1\u20098.0 \u03bcmol\/kgFFM\/min, <jats:italic>P<\/jats:italic>\u2009&lt;\u2009.06) compared to controls. Increases in total fat (\u22123.9\u2009\u00b1\u20097.5 vs 10.5\u2009\u00b1\u20098.4 \u03bcmol\/kgFFM\/min, <jats:italic>P<\/jats:italic>\u2009&lt;\u2009.0001) and plasma fatty acid oxidation rates (0.0\u2009\u00b1\u20091.8 vs 5.1\u2009\u00b1\u20093.9 \u03bcmol\/kgFFM\/min, <jats:italic>P<\/jats:italic>\u2009&lt;\u2009.0001) from rest to exercise were severely blunted in BTHS compared to controls. Conclusion: An inability to upregulate fat metabolism during moderate intensity exercise appears to be partially compensated by elevations in glucose metabolism. Derangements in fat and glucose metabolism are characteristic of the pathophysiology of BTHS.<\/jats:p><jats:p>A severely blunted ability to upregulate fat metabolism during a modest level of physical activity is a defining pathophysiologic characteristic in children, adolescents, and young adults with BTHS.<\/jats:p>","DOI":"10.1002\/jimd.12094","type":"journal-article","created":{"date-parts":[[2019,3,29]],"date-time":"2019-03-29T14:45:40Z","timestamp":1553870740000},"page":"480-493","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Blunted fat oxidation upon submaximal exercise is partially compensated by enhanced glucose metabolism in children, adolescents, and young adults with Barth syndrome"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2329-7623","authenticated-orcid":false,"given":"William Todd","family":"Cade","sequence":"first","affiliation":[{"name":"Program in Physical Therapy Washington University School of Medicine  St. Louis Missouri"},{"name":"Department of Medicine Washington University School of Medicine  St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn L.","family":"Bohnert","sequence":"additional","affiliation":[{"name":"Program in Physical Therapy Washington University School of Medicine  St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda R.","family":"Peterson","sequence":"additional","affiliation":[{"name":"Department of Medicine Washington University School of Medicine  St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce W.","family":"Patterson","sequence":"additional","affiliation":[{"name":"Department of Medicine Washington University School of Medicine  St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam 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Radiology Washington University School of Medicine  St. Louis Missouri"},{"name":"Department of Electrical and Computer Engineering Auburn University  Auburn Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George G.","family":"Schweitzer","sequence":"additional","affiliation":[{"name":"Department of Medicine Washington University School of Medicine  St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaji K.","family":"Chacko","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Baylor College of Medicine  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald J.","family":"Wanders","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina A.","family":"Pacak","sequence":"additional","affiliation":[{"name":"Department of Pediatrics 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Paper presented at: Barth Syndrome Foundation Scientific Medical & Family Conference;2018; Clearwater Beach FL."},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410400416"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2013.05.007"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1996.270.2.E259"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1991.260.6.E927"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00282.2014"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1185\/03007990903533681"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-199604000-00012"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.292.18.2227"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.hjh.0000209993.26057.de"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.12094","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jimd.12094","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.12094","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T08:31:41Z","timestamp":1694334701000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jimd.12094"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,11]]},"references-count":44,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019,5]]}},"alternative-id":["10.1002\/jimd.12094"],"URL":"https:\/\/doi.org\/10.1002\/jimd.12094","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,11]]},"assertion":[{"value":"2018-11-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-04-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}