{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T22:38:33Z","timestamp":1790375913069,"version":"4.1.0"},"reference-count":44,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2017,8,21]],"date-time":"2017-08-21T00:00:00Z","timestamp":1503273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Recent work has suggested that fibroblast growth factor-21 (FGF-21) is a useful biomarker of mitochondrial disease (MD). We routinely measured FGF-21 levels on patients who were investigated at our centre for MD and evaluated its diagnostic performance based on detailed genetic and other laboratory findings. Patients\u2019 FGF-21 results were assessed by the use of age-adjusted z-scores based on normalised FGF-21 values from a healthy population. One hundred and fifty five patients were investigated. One hundred and four of these patients had molecular evidence for MD, 27 were deemed to have disorders other than MD (non-MD), and 24 had possible MD. Patients with defects in mitochondrial DNA (mtDNA) maintenance (n = 32) and mtDNA rearrangements (n = 17) had the highest median FGF-21 among the MD group. Other MD patients harbouring mtDNA point mutations (n = 40) or mutations in other autosomal genes (n = 7) and those with partially characterised MD had lower FGF-21 levels. The area under the receiver operating characteristic curve for distinguishing MD from non-MD patients was 0.69. No correlation between FGF-21 and creatinine, creatine kinase, or cardio-skeletal myopathy score was found. FGF-21 was significantly associated with plasma lactate and ocular myopathy. Although FGF-21 was found to have a low sensitivity for detecting MD, at a z-score of 2.8, its specificity was above 90%. We suggest that a high serum concentration of FGF-21 would be clinically useful in MD, especially in adult patients with chronic progressive external ophthalmoplegia, and may enable bypassing muscle biopsy and directly opting for genetic analysis. Availability of its assay has thus modified our diagnostic pathway.<\/jats:p>","DOI":"10.3390\/jcm6080080","type":"journal-article","created":{"date-parts":[[2017,8,21]],"date-time":"2017-08-21T11:10:51Z","timestamp":1503313851000},"page":"80","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Use of FGF-21 as a Biomarker of Mitochondrial Disease in Clinical Practice"],"prefix":"10.3390","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5832-7992","authenticated-orcid":false,"given":"Alireza","family":"Morovat","sequence":"first","affiliation":[{"name":"Department of Clinical Biochemistry, Oxford University Hospitals, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gayani","family":"Weerasinghe","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Oxford University Hospitals, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Nesbitt","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, The Children\u2019s Hospital, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Hofer","sequence":"additional","affiliation":[{"name":"Department of Neuropathology and Ocular Pathology, West Wing, Oxford University Hospitals, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Agnew","sequence":"additional","affiliation":[{"name":"Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geralrine","family":"Quaghebeur","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, West Wing, Oxford University Hospitals, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Sergeant","sequence":"additional","affiliation":[{"name":"NHS Specialised Services for Rare Mitochondrial Disorders of Adults and Children UK, Oxford Medical Genetics Laboratories, Oxford University Hospitals, Oxford OX3 7LE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7125-5391","authenticated-orcid":false,"given":"Carl","family":"Fratter","sequence":"additional","affiliation":[{"name":"NHS Specialised Services for Rare Mitochondrial Disorders of Adults and Children UK, Oxford Medical Genetics Laboratories, Oxford University Hospitals, Oxford OX3 7LE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nishan","family":"Guha","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Oxford University Hospitals, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Mirzazadeh","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Oxford University Hospitals, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Poulton","sequence":"additional","affiliation":[{"name":"Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,8,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.mito.2006.12.004","article-title":"Population prevalence of the MELAS A3243G mutation","volume":"7","author":"Manwaring","year":"2007","journal-title":"Mitochondrion"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1093\/brain\/awg170","article-title":"Minimum birth prevalence of mitochondrial respiratory chain disorders in children","volume":"126","author":"Skladal","year":"2003","journal-title":"Brain"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1002\/ana.24362","article-title":"Prevalence of nuclear and mitochondrial DNA mutations related to adult mitochondrial disease","volume":"77","author":"Gorman","year":"2015","journal-title":"Ann. 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