{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T02:51:57Z","timestamp":1791427917840,"version":"4.3.3"},"reference-count":24,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,10,14]],"date-time":"2015-10-14T00:00:00Z","timestamp":1444780800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology (MEXT)","doi-asserted-by":"crossref","award":["25461571 (to Y.K.)"],"award-info":[{"award-number":["25461571 (to Y.K.)"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology (MEXT)","doi-asserted-by":"crossref","award":["25860891 (to S.Y.)"],"award-info":[{"award-number":["25860891 (to S.Y.)"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology (MEXT)","doi-asserted-by":"crossref","award":["25242062 (to M.T.)"],"award-info":[{"award-number":["25242062 (to M.T.)"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The Ministry of Health, Labor and Welfare of Japan.","award":["24-Nanchi-Ippan-005 (to Y.K.) for Research on Intractable Diseases"],"award-info":[{"award-number":["24-Nanchi-Ippan-005 (to Y.K.) for Research on Intractable Diseases"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The diagnosis of mitochondrial disorders (MDs) is occasionally difficult because patients often present with solitary, or a combination of, symptoms caused by each organ insufficiency, which may be the result of respiratory chain enzyme deficiency. Growth differentiation factor 15 (GDF\u201015) has been reported to be elevated in serum of patients with MDs. In this study, we investigated whether GDF\u201015 is a more useful biomarker for MDs than several conventional biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We measured the serum levels of GDF\u201015 and fibroblast growth factor 21 (FGF\u201021), as well as other biomarkers, in 48 MD patients and in 146 healthy controls in Japan. GDF\u201015 and FGF\u201021 concentrations were measured by enzyme\u2010linked immunosorbant assay and compared with lactate, pyruvate, creatine kinase, and the lactate\u2010to\u2010pyruvate ratio. We calculated sensitivity and specificity and also evaluated the correlation based on two rating scales, including the Newcastle Mitochondrial Disease Rating Scale (NMDAS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Mean GDF\u201015 concentration was 6\u2010fold higher in MD patients compared to healthy controls (2,711 \u00b1 2,459 pg\/ml vs 462.5 \u00b1 141.0 pg\/mL;\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001). Using a receiver operating characteristic curve, the area under the curve was significantly higher for GDF\u201015 than FGF\u201021 and other conventional biomarkers. Our date suggest that GDF\u201015 is the most useful biomarker for MDs of the biomarkers examined, and it is associated with MD severity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Our results suggest that measurement of GDF\u201015 is the most useful first\u2010line test to indicate the patients who have the mitochondrial respiratory chain deficiency. Ann Neurol 2015;78:Ann Neurol 2015;78:679\u2013696<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.24506","type":"journal-article","created":{"date-parts":[[2015,10,14]],"date-time":"2015-10-14T08:28:18Z","timestamp":1444811298000},"page":"814-823","source":"Crossref","is-referenced-by-count":297,"title":["Growth differentiation factor 15 as a useful biomarker for mitochondrial disorders"],"prefix":"10.1002","volume":"78","author":[{"given":"Shuichi","family":"Yatsuga","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Child Health Kurume University School of Medicine Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasunori","family":"Fujita","sequence":"additional","affiliation":[{"name":"Research Team for Mechanism of Aging Tokyo Metropolitan Institute of Gerontology Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Ishii","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine University of Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Fukumoto","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Internal Medicine Kurume University School of Medicine Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajime","family":"Arahata","sequence":"additional","affiliation":[{"name":"Department of Neurology, Neuro\u2010Muscular Center National Omuta Hospital Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuyuki","family":"Kakuma","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Kurume University Graduate School of Medicine Kurume Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshio","family":"Kojima","sequence":"additional","affiliation":[{"name":"Health Care Center Toyohashi University of Technology Toyohashi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Ito","sequence":"additional","affiliation":[{"name":"Research Team for Mechanism of Aging Tokyo Metropolitan Institute of Gerontology Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Genomics for Longevity and Health Tokyo Metropolitan Institute of Gerontology Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reo","family":"Saiki","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Child Health Kurume University School of Medicine Fukuoka 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