{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T23:37:19Z","timestamp":1790293039987,"version":"4.1.0"},"reference-count":22,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T00:00:00Z","timestamp":1698105600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["FOR2509"],"award-info":[{"award-number":["FOR2509"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["TH1461\/7\u20102"],"award-info":[{"award-number":["TH1461\/7\u20102"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteomics Clinical Apps"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>Congenital disorders of glycosylation (CDG) are one of the fastest growing groups of inborn errors of metabolism. Despite the availability of next\u2010generation sequencing techniques and advanced methods for evaluation of glycosylation, CDG screening mainly relies on the analysis of serum transferrin (Tf) by isoelectric focusing, HPLC or capillary electrophoresis. The main pitfall of this screening method is the presence of\u00a0Tf protein variants within the general population. Although\u00a0reports\u00a0describe the role of Tf variants leading to falsely abnormal results, their significance in confounding diagnosis in patients with CDG has not been documented so far. Here, we describe two PMM2\u2010CDG cases, in which Tf variants complicated the diagnostic.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Design<\/jats:title><jats:p>Glycosylation investigations included classical screening techniques (capillary electrophoresis, isoelectric focusing and HPLC of Tf) and various confirmation techniques (two\u2010dimensional electrophoresis, western blot,\u00a0<jats:italic>N\u2010<\/jats:italic>glycome, UPLC\u2010FLR\/QTOF MS with Rapifluor). Tf variants were highlighted following neuraminidase treatment. Sequencing of\u00a0<jats:italic>PMM2 was performed<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In both patients, Tf screening pointed to CDG\u2010II, while second\u2010line analyses pointed to CDG\u2010I. Tf variants were found in both patients, explaining these discrepancies.\u00a0<jats:italic>PMM2<\/jats:italic>\u00a0causative\u00a0variants were identified in both patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Clinical Relevance<\/jats:title><jats:p>We suggest that a neuraminidase treatment should be performed when a typical CDG Tf pattern is found upon initial screening analysis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/prca.202300040","type":"journal-article","created":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T05:10:07Z","timestamp":1698210607000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["\u201cHide and seek\u201d: Misleading transferrin variants in PMM2\u2010CDG complicate diagnostics"],"prefix":"10.1002","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2651-650X","authenticated-orcid":false,"given":"Alexandre","family":"Raynor","sequence":"first","affiliation":[{"name":"AP\u2010HP, Biochimie M\u00e9tabolique et Cellulaire H\u00f4pital Bichat  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Bruneel","sequence":"additional","affiliation":[{"name":"AP\u2010HP, Biochimie M\u00e9tabolique et Cellulaire H\u00f4pital Bichat  Paris France"},{"name":"INSERM UMR1193 Facult\u00e9 de Pharmacie Universit\u00e9 Paris\u2010Saclay b\u00e2timent Henri Moissan  Orsay France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter","family":"Vermeersch","sequence":"additional","affiliation":[{"name":"Clinical Department of Laboratory Medicine UZ Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Cholet","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris\u2010Saclay, CEA, INRAE, D\u00e9partement M\u00e9dicaments et Technologies pour la Sant\u00e9 (DMTS) MetaboHUB  Gif sur Yvette France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Friedrich","sequence":"additional","affiliation":[{"name":"Centre for Child and Adolescent Medicine Freiburg Department of General Paediatrics Adolescent Medicine and Neonatology  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Eckenweiler","sequence":"additional","affiliation":[{"name":"Department of Neuropediatrics and Muscle Disorders Centre for Child and Adolescent Medicine Freiburg  Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke","family":"Schumann","sequence":"additional","affiliation":[{"name":"Centre for 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