{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T04:58:14Z","timestamp":1774328294740,"version":"3.50.1"},"reference-count":19,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2013,10,1]],"date-time":"2013-10-01T00:00:00Z","timestamp":1380585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000871","name":"Mayo Clinic","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002108","name":"Friedreich Ataxia Research Alliance","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100002108","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005202","name":"Muscular Dystrophy Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005202","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["NIH RO1 AG15709"],"award-info":[{"award-number":["NIH RO1 AG15709"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,10,1]]},"abstract":"<jats:sec>\n                  <jats:title>BACKGROUND<\/jats:title>\n                  <jats:p>Friedreich ataxia (FRDA) is caused by reduced frataxin (FXN) concentrations. A clinical diagnosis is typically confirmed by DNA-based assays for GAA-repeat expansions or mutations in the FXN (frataxin) gene; however, these assays are not applicable to therapeutic monitoring and population screening. To facilitate the diagnosis and monitoring of FRDA patients, we developed an immunoassay for measuring FXN.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>Antibody pairs were used to capture FXN and an internal control protein, ceruloplasmin (CP), in 15 \u03bcL of whole blood (WB) or one 3-mm punch of a dried blood spot (DBS). Samples were assayed on a Luminex LX200 analyzer and validated according to standard criteria.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>The mean recovery of FXN from WB and DBS samples was 99%. Intraassay and interassay imprecision (CV) values were 4.9%\u201313% and 9.8%\u201316%, respectively. The FXN limit of detection was 0.07 ng\/mL, and the reportable range of concentrations was 2\u2013200 ng\/mL. Reference adult and pediatric FXN concentrations ranged from 15 to 82 ng\/mL (median, 33 ng\/mL) for DBS and WB. The FXN concentration range was 12\u201322 ng\/mL (median, 15 ng\/mL) for FRDA carriers and 1\u201326 ng\/mL (median 5 ng\/mL) for FRDA patients. Measurement of the FXN\/CP ratio increased the ability to distinguish between patients, carriers, and the reference population.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>This assay is applicable to the diagnosis and therapeutic monitoring of FRDA. This assay can measure FXN and the control protein CP in both WB and DBS specimens with minimal sample requirements, creating the potential for high-throughput population screening of FRDA.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1373\/clinchem.2013.207472","type":"journal-article","created":{"date-parts":[[2013,7,10]],"date-time":"2013-07-10T00:48:18Z","timestamp":1373417298000},"page":"1461-1469","source":"Crossref","is-referenced-by-count":11,"title":["High-Throughput Immunoassay for the Biochemical Diagnosis of Friedreich Ataxia in Dried Blood Spots and Whole Blood"],"prefix":"10.1093","volume":"59","author":[{"given":"Devin","family":"Oglesbee","sequence":"first","affiliation":[{"name":"Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, and"},{"name":"Departments of Medical Genetics"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles","family":"Kroll","sequence":"first","affiliation":[{"name":"Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oleksandr","family":"Gakh","sequence":"first","affiliation":[{"name":"Biochemistry and Molecular Biology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric C","family":"Deutsch","sequence":"first","affiliation":[{"name":"Departments of Neurology"},{"name":"Pediatrics, and"},{"name":"Pharmacology, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David R","family":"Lynch","sequence":"first","affiliation":[{"name":"Departments of Neurology"},{"name":"Pediatrics, and"},{"name":"Pharmacology, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralitza","family":"Gavrilova","sequence":"first","affiliation":[{"name":"Departments of Medical Genetics"},{"name":"Neurology, and"},{"name":"Pediatrics and Adolescent Medicine, Mayo Clinic College of Medicine, Rochester, MN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Tortorelli","sequence":"first","affiliation":[{"name":"Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimiyo","family":"Raymond","sequence":"first","affiliation":[{"name":"Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dimitar","family":"Gavrilov","sequence":"first","affiliation":[{"name":"Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, and"},{"name":"Pediatrics and Adolescent Medicine, Mayo Clinic College of Medicine, Rochester, MN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piero","family":"Rinaldo","sequence":"first","affiliation":[{"name":"Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, and"},{"name":"Pediatrics and Adolescent Medicine, Mayo Clinic College of Medicine, Rochester, MN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dietrich","family":"Matern","sequence":"first","affiliation":[{"name":"Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, and"},{"name":"Departments of Medical Genetics"},{"name":"Pediatrics and Adolescent Medicine, Mayo Clinic College of Medicine, Rochester, MN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grazia","family":"Isaya","sequence":"first","affiliation":[{"name":"Biochemistry and Molecular Biology"},{"name":"Pediatrics and Adolescent Medicine, Mayo Clinic College of Medicine, Rochester, MN"},{"name":"Mayo Clinic Children's Center, Rochester, MN"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2013,10,1]]},"reference":[{"key":"2020022705343964300_B1","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1093\/brain\/104.3.589","article-title":"Friedreich's ataxia: a clinical and genetic study of 90 families with an analysis of early diagnostic criteria and intrafamilial clustering of clinical features","volume":"104","author":"Harding","year":"1981","journal-title":"Brain"},{"key":"2020022705343964300_B2","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1002\/mds.22912","article-title":"Measuring the rate of progression in Friedreich ataxia: implications for clinical trial design","volume":"25","author":"Friedman","year":"2010","journal-title":"Mov Disord"},{"key":"2020022705343964300_B3","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1177\/0883073812448535","article-title":"Cardiomyopathy in Friedreich ataxia: clinical findings and research","volume":"27","author":"Payne","year":"2012","journal-title":"J Child Neurol"},{"key":"2020022705343964300_B4","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.jns.2011.05.023","article-title":"Mortality in Friedreich ataxia","volume":"307","author":"Tsou","year":"2011","journal-title":"J Neurol Sci"},{"key":"2020022705343964300_B5","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.mcn.2012.08.003","article-title":"Iron-sulfur cluster synthesis, iron homeostasis and oxidative stress in Friedreich ataxia","volume":"55","author":"Vaubel","year":"2013","journal-title":"Mol Cell Neurosci"},{"key":"2020022705343964300_B6","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1177\/0883073812453872","article-title":"A review of Friedreich ataxia clinical trial results","volume":"27","author":"Perlman","year":"2012","journal-title":"J Child Neurol"},{"key":"2020022705343964300_B7","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1007\/s00246-011-9943-6","article-title":"Cardiomyopathy of Friedreich's ataxia: use of mouse models to understand human disease and guide therapeutic development","volume":"32","author":"Payne","year":"2011","journal-title":"Pediatr Cardiol"},{"key":"2020022705343964300_B8","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1001\/archneurol.2011.834","article-title":"Exonic deletions of FXN and early-onset Friedreich ataxia","volume":"69","author":"Anheim","year":"2012","journal-title":"Arch Neurol"},{"key":"2020022705343964300_B9","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1177\/0883073812449691","article-title":"Therapeutic developments in Friedreich ataxia","volume":"27","author":"Wilson","year":"2012","journal-title":"J Child Neurol"},{"key":"2020022705343964300_B10","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.ymgme.2008.03.019","article-title":"Lateral-flow immunoassay for the frataxin protein in Friedreich's ataxia patients and carriers","volume":"94","author":"Willis","year":"2008","journal-title":"Mol Genet Metab"},{"key":"2020022705343964300_B11","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.ymgme.2010.07.001","article-title":"A rapid, noninvasive immunoassay for frataxin: utility in assessment of Friedreich ataxia","volume":"101","author":"Deutsch","year":"2010","journal-title":"Mol Genet Metab"},{"key":"2020022705343964300_B12","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.aca.2009.11.036","article-title":"A high throughput electrochemiluminescence assay for the quantification of frataxin protein levels","volume":"659","author":"Steinkellner","year":"2010","journal-title":"Anal Chim Acta"},{"key":"2020022705343964300_B13","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1002\/mds.23789","article-title":"Correlation of frataxin content in blood and skeletal muscle endorses frataxin as a biomarker in Friedreich ataxia","volume":"26","author":"Nachbauer","year":"2011","journal-title":"Mov Disord"},{"key":"2020022705343964300_B14","doi-asserted-by":"crossref","first-page":"38486","DOI":"10.1074\/jbc.M110.145144","article-title":"Normal and Friedreich ataxia cells express different isoforms of frataxin with complementary roles in iron-sulfur cluster assembly","volume":"285","author":"Gakh","year":"2010","journal-title":"J Biol Chem"},{"key":"2020022705343964300_B15","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.ymgme.2006.03.008","article-title":"Retrospective determination of ceruloplasmin in newborn screening blood spots of patients with Wilson disease","volume":"89","author":"Kroll","year":"2006","journal-title":"Mol Genet Metab"},{"key":"2020022705343964300_B16","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1038\/gim.2012.2","article-title":"Enhanced interpretation of newborn screening results without analyte cutoff values","volume":"14","author":"Marquardt","year":"2012","journal-title":"Genet Med"},{"key":"2020022705343964300_B17","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1016\/S1474-4422(07)70220-X","article-title":"Neurological effects of high-dose idebenone in patients with Friedreich's ataxia: a randomised, placebo-controlled trial","volume":"6","author":"Di Prospero","year":"2007","journal-title":"Lancet Neurol"},{"key":"2020022705343964300_B18","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1182\/blood-2006-12-065433","article-title":"Selective iron chelation in Friedreich ataxia: biologic and clinical implications","volume":"110","author":"Boddaert","year":"2007","journal-title":"Blood"},{"key":"2020022705343964300_B19","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1136\/heart.87.4.346","article-title":"Idebenone and reduced cardiac hypertrophy in Friedreich's ataxia","volume":"87","author":"Hausse","year":"2002","journal-title":"Heart"}],"container-title":["Clinical Chemistry"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/clinchem\/article-pdf\/59\/10\/1461\/32661282\/clinchem1461.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/clinchem\/article-pdf\/59\/10\/1461\/32661282\/clinchem1461.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,2,27]],"date-time":"2020-02-27T05:36:57Z","timestamp":1582781817000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/clinchem\/article\/59\/10\/1461\/5622083"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,10,1]]},"references-count":19,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2013,10,1]]},"published-print":{"date-parts":[[2013,10,1]]}},"URL":"https:\/\/doi.org\/10.1373\/clinchem.2013.207472","relation":{},"ISSN":["0009-9147","1530-8561"],"issn-type":[{"value":"0009-9147","type":"print"},{"value":"1530-8561","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2013,10,1]]},"published":{"date-parts":[[2013,10,1]]}}}