title: Serum FGF21 levels in adult m.3243A>G carriers: clinical implications.
abstract: OBJECTIVE
  To determine the value of fibroblast growth factor 21 (FGF21), a recently discovered biomarker for mitochondrial disease, in predicting clinical disease severity and disease progression in adult carriers of the m.3243A>G mutation.
  
  
  METHODS
  In the context of a national inventory, the heteroplasmy levels of the m.3243A>G mutation were measured in leukocytes and urinary epithelial cells. The Newcastle Mitochondrial Disease Adult Scale score was determined and blood was drawn for measuring FGF21 concentration. Twenty-five of the included initial patients studied were then selected randomly for a follow-up study.
  
  
  RESULTS
  This prognostic study included 99 adult carriers of the m.3243A>G mutation. Our analysis revealed a moderate, significant correlation between FGF21 concentration and disease severity (r = 0.49; p = <0.001). No significant correlations were found between disease severity and the heteroplasmy percentage determined in urinary epithelial cells or the heteroplasmy percentage determined in leukocytes. Weak but significant correlations were also found between FGF21 concentration and the severity of the myopathy (r = 0.38; p = <0.001) and between the concentration of FGF21 and the severity of the encephalopathy (r = 0.30; p = <0.001). Repeated measurements following 25 subjects for 2 years revealed no significant correlation between FGF21 concentration and disease progression.
  
  
  CONCLUSIONS
  Measuring FGF21 concentration had little added value in monitoring and predicting the disease course in this specific patient group.
authors.affiliation: From the Department of Pediatrics, Radboud University Nijmegen Medical Centre, Nijmegen Centre for Mitochondrial Disorders (S.K., P.d.L., R.J.T.R., M.C.H.J., J.A.M.S.), and Departments of Laboratory Medicine (D.H.v.T., A.M.B., F.C.G.J.S.), Radiology and Nuclear Medicine (D.V.), Health Evidence (A.R.T.D.), and General Internal Medicine (M.C.H.J.), Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands. saskia.koene@radboudumc.nl.
authors.forename: Saskia
authors.initials: S
authors.lastname: Koene
authors.affiliation: From the Department of Pediatrics, Radboud University Nijmegen Medical Centre, Nijmegen Centre for Mitochondrial Disorders (S.K., P.d.L., R.J.T.R., M.C.H.J., J.A.M.S.), and Departments of Laboratory Medicine (D.H.v.T., A.M.B., F.C.G.J.S.), Radiology and Nuclear Medicine (D.V.), Health Evidence (A.R.T.D.), and General Internal Medicine (M.C.H.J.), Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: de Laat
authors.affiliation: From the Department of Pediatrics, Radboud University Nijmegen Medical Centre, Nijmegen Centre for Mitochondrial Disorders (S.K., P.d.L., R.J.T.R., M.C.H.J., J.A.M.S.), and Departments of Laboratory Medicine (D.H.v.T., A.M.B., F.C.G.J.S.), Radiology and Nuclear Medicine (D.V.), Health Evidence (A.R.T.D.), and General Internal Medicine (M.C.H.J.), Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
authors.forename: Doorlène H
authors.initials: DH
authors.lastname: van Tienoven
authors.affiliation: From the Department of Pediatrics, Radboud University Nijmegen Medical Centre, Nijmegen Centre for Mitochondrial Disorders (S.K., P.d.L., R.J.T.R., M.C.H.J., J.A.M.S.), and Departments of Laboratory Medicine (D.H.v.T., A.M.B., F.C.G.J.S.), Radiology and Nuclear Medicine (D.V.), Health Evidence (A.R.T.D.), and General Internal Medicine (M.C.H.J.), Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
authors.forename: Dennis
authors.initials: D
authors.lastname: Vriens
authors.affiliation: From the Department of Pediatrics, Radboud University Nijmegen Medical Centre, Nijmegen Centre for Mitochondrial Disorders (S.K., P.d.L., R.J.T.R., M.C.H.J., J.A.M.S.), and Departments of Laboratory Medicine (D.H.v.T., A.M.B., F.C.G.J.S.), Radiology and Nuclear Medicine (D.V.), Health Evidence (A.R.T.D.), and General Internal Medicine (M.C.H.J.), Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
authors.forename: André M
authors.initials: AM
authors.lastname: Brandt
authors.affiliation: From the Department of Pediatrics, Radboud University Nijmegen Medical Centre, Nijmegen Centre for Mitochondrial Disorders (S.K., P.d.L., R.J.T.R., M.C.H.J., J.A.M.S.), and Departments of Laboratory Medicine (D.H.v.T., A.M.B., F.C.G.J.S.), Radiology and Nuclear Medicine (D.V.), Health Evidence (A.R.T.D.), and General Internal Medicine (M.C.H.J.), Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
authors.forename: Fred C G J
authors.initials: FC
authors.lastname: Sweep
authors.affiliation: From the Department of Pediatrics, Radboud University Nijmegen Medical Centre, Nijmegen Centre for Mitochondrial Disorders (S.K., P.d.L., R.J.T.R., M.C.H.J., J.A.M.S.), and Departments of Laboratory Medicine (D.H.v.T., A.M.B., F.C.G.J.S.), Radiology and Nuclear Medicine (D.V.), Health Evidence (A.R.T.D.), and General Internal Medicine (M.C.H.J.), Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
authors.forename: Richard J T
authors.initials: RJ
authors.lastname: Rodenburg
authors.affiliation: From the Department of Pediatrics, Radboud University Nijmegen Medical Centre, Nijmegen Centre for Mitochondrial Disorders (S.K., P.d.L., R.J.T.R., M.C.H.J., J.A.M.S.), and Departments of Laboratory Medicine (D.H.v.T., A.M.B., F.C.G.J.S.), Radiology and Nuclear Medicine (D.V.), Health Evidence (A.R.T.D.), and General Internal Medicine (M.C.H.J.), Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
authors.forename: A Rogier T
authors.initials: AR
authors.lastname: Donders
authors.affiliation: From the Department of Pediatrics, Radboud University Nijmegen Medical Centre, Nijmegen Centre for Mitochondrial Disorders (S.K., P.d.L., R.J.T.R., M.C.H.J., J.A.M.S.), and Departments of Laboratory Medicine (D.H.v.T., A.M.B., F.C.G.J.S.), Radiology and Nuclear Medicine (D.V.), Health Evidence (A.R.T.D.), and General Internal Medicine (M.C.H.J.), Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
authors.forename: Mirian C H
authors.initials: MC
authors.lastname: Janssen
authors.affiliation: From the Department of Pediatrics, Radboud University Nijmegen Medical Centre, Nijmegen Centre for Mitochondrial Disorders (S.K., P.d.L., R.J.T.R., M.C.H.J., J.A.M.S.), and Departments of Laboratory Medicine (D.H.v.T., A.M.B., F.C.G.J.S.), Radiology and Nuclear Medicine (D.V.), Health Evidence (A.R.T.D.), and General Internal Medicine (M.C.H.J.), Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
authors.forename: Jan A M
authors.initials: JA
authors.lastname: Smeitink
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005346:Fibroblast Growth Factors / Q000097:blood* / Q000235:genetics*; D005500:Follow-Up Studies; D006579:Heterozygote; D006801:Humans; D007962:Leukocytes / Q000737:chemistry; D008297:Male; D028361:Mitochondrial Diseases / Q000097:blood* / Q000235:genetics*; D017237:Mitochondrial Encephalomyopathies / Q000097:blood / Q000235:genetics; D017240:Mitochondrial Myopathies / Q000097:blood / Q000235:genetics; D009154:Mutation / Q000235:genetics; D011379:Prognosis
chemical_list: D015415:Biomarkers; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors