{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:23:17Z","timestamp":1790875397339,"version":"4.1.0"},"reference-count":18,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,1,4]],"date-time":"2021-01-04T00:00:00Z","timestamp":1609718400000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Centre for Clinical Treatment Research"},{"name":"The Research Council of Norway","award":["288164"],"award-info":[{"award-number":["288164"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The aim of this study was to explore the utility of the serum biomarkers neurofilament light chain, fibroblast growth factor 21 and growth and differentiation factor 15 in diagnosing primary mitochondrial disorders. We measured serum neurofilament light chain, fibroblast growth factor 21 and growth and differentiation factor 15 in 26 patients with a genetically proven mitochondrial disease. Fibroblast growth factor 21 and growth and differentiation factor 15 were measured by enzyme-linked immunosorbent assay and neurofilament light chain with the Simoa assay. Neurofilament light chain was highest in patients with multi-systemic involvement that included the central nervous system such as those with the m.3242A&amp;gt;G mutation. Mean neurofilament light chain was also highest in patients with epilepsy versus those without [49.74\u2009pg\/ml versus 19.7\u2009pg\/ml (P\u2009=\u20090.015)], whereas fibroblast growth factor 21 and growth and differentiation factor 15 levels were highest in patients with prominent myopathy, such as those with single-mitochondrial DNA deletion. Our results suggest that the combination of neurofilament light chain, fibroblast growth factor 21 and growth and differentiation factor 15 is useful in the diagnostic evaluation of mitochondrial disease. Growth and differentiation factor 15 and fibroblast growth factor 21 identify those with muscle involvement, whereas neurofilament light chain is a clear marker for central nervous system involvement independent of underlying mitochondrial pathology. Levels of neurofilament light chain appear to correlate with the degree of ongoing damage suggesting, therefore, that monitoring neurofilament light chain levels may provide prognostic information and a way of monitoring disease activity.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaa222","type":"journal-article","created":{"date-parts":[[2021,1,4]],"date-time":"2021-01-04T17:56:56Z","timestamp":1609783016000},"source":"Crossref","is-referenced-by-count":31,"title":["Serum biomarkers in primary mitochondrial disorders"],"prefix":"10.1093","volume":"3","author":[{"given":"Kristin N","family":"Varhaug","sequence":"first","affiliation":[{"name":"Department of Neurology, Haukeland University Hospital, Bergen, Norway"},{"name":"Department of Clinical Medicine, University of Bergen, Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Hikmat","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, University of Bergen, Bergen, Norway"},{"name":"Department of Paediatrics and Adolescents, Haukeland University Hospital, Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanne Linda","family":"Nakkestad","sequence":"additional","affiliation":[{"name":"Department of Neurology, Haukeland University Hospital, Bergen, Norway"},{"name":"Department of Neurology, Neuro-SysMed, Haukeland University Hospital, Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian A","family":"Vedeler","sequence":"additional","affiliation":[{"name":"Department of Neurology, Haukeland University Hospital, Bergen, Norway"},{"name":"Department of Clinical Medicine, University of Bergen, Bergen, Norway"},{"name":"Department of Neurology, Neuro-SysMed, Haukeland University Hospital, Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence A","family":"Bindoff","sequence":"additional","affiliation":[{"name":"Department of Neurology, Haukeland University Hospital, Bergen, Norway"},{"name":"Department of Clinical Medicine, University of Bergen, Bergen, Norway"},{"name":"Department of Neurology, Neuro-SysMed, Haukeland University Hospital, Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,1,4]]},"reference":[{"key":"2021011707244125100_fcaa222-B1","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1042\/EBC20170111","article-title":"Biomarkers for mitochondrial energy metabolism diseases","volume":"62","author":"Boenzi","year":"2018","journal-title":"Essays Biochem"},{"key":"2021011707244125100_fcaa222-B2","doi-asserted-by":"crossref","first-page":"2010","DOI":"10.1212\/WNL.0000000000002705","article-title":"A comparison of current serum biomarkers as diagnostic indicators of mitochondrial diseases","volume":"86","author":"Davis","year":"2016","journal-title":"Neurology"},{"key":"2021011707244125100_fcaa222-B3","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1002\/ana.24954","article-title":"Serum neurofilament light: a biomarker of neuronal damage in multiple sclerosis","volume":"81","author":"Disanto","year":"2017","journal-title":"Ann Neurol"},{"key":"2021011707244125100_fcaa222-B4","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1093\/brain\/awn007","article-title":"POLG1 mutations cause a syndromic epilepsy with occipital lobe predilection","volume":"131","author":"Engelsen","year":"2008","journal-title":"Brain"},{"key":"2021011707244125100_fcaa222-B5","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/1471-2164-15-91","article-title":"Transcriptomic profiling of TK2 deficient human skeletal muscle suggests a role for the p53 signalling pathway and identifies growth and differentiation factor-15 as a potential novel biomarker for mitochondrial myopathies","volume":"15","author":"Kalko","year":"2014","journal-title":"BMC Genomics"},{"key":"2021011707244125100_fcaa222-B6","doi-asserted-by":"crossref","first-page":"2290","DOI":"10.1212\/WNL.0000000000003374","article-title":"FGF21 is a biomarker for mitochondrial translation and mtDNA maintenance disorders","volume":"87","author":"Lehtonen","year":"2016","journal-title":"Neurology"},{"key":"2021011707244125100_fcaa222-B7","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1016\/j.nmd.2017.08.006","article-title":"International Workshop:: outcome measures and clinical trial readiness in primary mitochondrial myopathies in children and adults. 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