{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T10:29:25Z","timestamp":1794047365353,"version":"4.8.0"},"reference-count":22,"publisher":"Ferrata Storti Foundation (Haematologica)","issue":"10","license":[{"start":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T00:00:00Z","timestamp":1599696000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["haematol"],"abstract":"<jats:p>The diagnostic evaluation and clinical characterization of rare hereditary anemia (RHA) is to date still challenging. In particular, there is little knowledge of the broad metabolic impact of many of the molecular defects underlying RHA. In this study we explored the potential of untargeted metabolomics to diagnose a relatively common type of RHA: pyruvate kinase deficiency (PKD). In total, 1,903 unique metabolite features were identified in dried blood spot samples from 16 PKD patients and 32 healthy controls. A metabolic fingerprint was identified using a machine learning algorithm, and subsequently a binary classification model was designed. The model showed high performance characteristics (AUC 0.990, 95% CI: 0.981-0.999) and an accurate class assignment was achieved for all newly added control (n=13) and patient samples, (n=6) with the exception of one patient (accuracy 94%). Important metabolites in the metabolic fingerprint included glycolytic intermediates, polyamines and several acyl carnitines. In general, the application of untargeted metabolomics in dried blood spots is a novel functional tool that holds promise for the diagnostic stratification and studies on the disease pathophysiology in RHA.<\/jats:p>","DOI":"10.3324\/haematol.2020.266957","type":"journal-article","created":{"date-parts":[[2020,9,16]],"date-time":"2020-09-16T14:40:44Z","timestamp":1600267244000},"page":"2720-2725","source":"Crossref","is-referenced-by-count":19,"title":["Untargeted metabolic profiling in dried blood spots identifies disease fingerprint for pyruvate kinase deficiency"],"prefix":"10.3324","volume":"106","author":[{"given":"Birgit","family":"Van Dooijeweert","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa H.","family":"Broeks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanda M.","family":"Verhoeven-Duif","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduard J.","family":"Van Beers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward E.S.","family":"Nieuwenhuis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wouter W.","family":"Van Solinge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marije","family":"Bartels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith J.","family":"Jans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Van Wijk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1856","published-online":{"date-parts":[[2020,9,10]]},"reference":[{"key":"30246","doi-asserted-by":"crossref","unstructured":"Da Costa L, Narla A, Mohandas N. An update on the pathogenesis and diagnosis of Diamond-Blackfan anemia. F1000Res. 2018; 7:F1000.","DOI":"10.12688\/f1000research.15542.1"},{"key":"30247","doi-asserted-by":"crossref","unstructured":"Grace RF, Zanella A, Neufeld EJ. Erythrocyte pyruvate kinase deficiency: 2015 status report. Am J Hematol. 2015; 90(9):825-830.","DOI":"10.1002\/ajh.24088"},{"key":"30248","doi-asserted-by":"crossref","unstructured":"Albuisson J, Murthy SE, Bandell M. Dehydrated hereditary stomatocytosis linked to gain-of-function mutations in mechanically activated PIEZO1 ion channels. Nat Commun. 2013; 4:1884.","DOI":"10.1038\/ncomms2899"},{"key":"30249","doi-asserted-by":"crossref","unstructured":"Roy NBA, Babbs C. The pathogenesis, diagnosis and management of congenital dyserythropoietic anaemia type I. Br J Haematol. 2019; 185(3):436-449.","DOI":"10.1111\/bjh.15817"},{"key":"30250","doi-asserted-by":"crossref","unstructured":"Vercellati C, Marcello AP, Fermo E, Barcellini W, Zanella A, Bianchi P. 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