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Dolichol serves as a carrier for glycan precursors or monosaccharides in N\u2010linked glycosylation. Pathogenic variants in\n                    <jats:italic>SRD5A3<\/jats:italic>\n                    can result in a congenital disorder of glycosylation (CDG), SRD5A3\u2010CDG, which is inherited in an autosomal recessive manner. Most plasma proteins are glycosylated and changes in the glycosylation of several glycoproteins are associated with pathological consequences. Despite the critical role of SRD5A3 in glycosylation, the impact of its deficiency on the glycosylation of serum proteins remains largely unexplored. In this study, we used tandem mass tag\u2010based multiplexed quantitative approach to analyze serum N\u2010glycoproteomics and proteomics in SRD5A3\u2010CDG patients and controls. We quantified 2200 serum N\u2010glycopeptides from 359\u2009N\u2010glycosites from 204 serum proteins. Extensive hypoglycosylation of serum proteins was observed in patients, with 245 of 291 altered glycopeptides decreased in SRD5A3\u2010CDG. Altered glycopeptides included those derived from haptoglobin, plasma serine protease inhibitor, alpha\u20101\u2010B glycoprotein, alpha\u20102\u2010macroglobulin, and ceruloplasmin. Some of these proteins have previously been reported to be associated with liver dysfunction, anemia, and coagulopathy, which could underlie similar clinical features observed in SRD5A3\u2010CDG patients. Overall, our study provides novel insights into alterations in the glycosylation status of specific serum proteins in SRD5A3\u2010CDG. Some of these alterations could be further pursued to develop glycopeptide\u2010based biomarkers as the current diagnosis of SRD5A3\u2010CDG by screening assays remains challenging. In addition, knowledge of altered glycoproteins could enhance our understanding of the disease spectrum and potentially unveil additional therapeutic avenues.\n                  <\/jats:p>","DOI":"10.1002\/jimd.70163","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:13:57Z","timestamp":1773015237000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Extensive Hypoglycosylation of Serum N\u2010Glycoproteins in\n                    <scp>SRD5A3<\/scp>\n                    Deficiency"],"prefix":"10.1002","volume":"49","author":[{"given":"Anu","family":"Jain","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohit","family":"Budhraja","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2759-609X","authenticated-orcid":false,"given":"Kishore","family":"Garapati","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester Minnesota USA"},{"name":"Manipal Academy of Higher Education (MAHE)  Manipal Karnataka India"},{"name":"Institute of Bioinformatics International Technology Park  Bangalore Karnataka India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4705-6434","authenticated-orcid":false,"given":"Christina","family":"Lam","sequence":"additional","affiliation":[{"name":"Norcliffe Foundation Center for Integrative Brain Research Seattle Children's Research Institute  Seattle Washington USA"},{"name":"Division of Genetic Medicine, Department of Pediatrics University of Washington School of Medicine  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Schultz","sequence":"additional","affiliation":[{"name":"Biochemical Genetics Laboratory, Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6915-4364","authenticated-orcid":false,"given":"Tamas","family":"Kozicz","sequence":"additional","affiliation":[{"name":"Biochemical Genetics Laboratory, Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester Minnesota USA"},{"name":"Department of Clinical Genomics Mayo Clinic  Rochester Minnesota USA"},{"name":"Department of Anatomy University of Pecs Medical School  Pecs Hungary"},{"name":"Department of Genomics and Genetic Sciences Ichan School of Medicine at Mount Sinai Hospital  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Morava","sequence":"additional","affiliation":[{"name":"Biochemical Genetics Laboratory, Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester Minnesota USA"},{"name":"Department of Clinical Genomics Mayo Clinic  Rochester Minnesota USA"},{"name":"Department of Genomics and Genetic Sciences Ichan School of Medicine at Mount Sinai Hospital  New York New York USA"},{"name":"Department of Biophysics University of P\u00e9cs, Medical School  P\u00e9cs Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9943-6127","authenticated-orcid":false,"given":"Akhilesh","family":"Pandey","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester Minnesota USA"},{"name":"Center for Individualized Medicine Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,24]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-00294-x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/12.4.43R"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10719-015-9626-2"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.5483\/BMBRep.2011.44.12.772"},{"key":"e_1_2_9_6_1","volume-title":"Essentials of Glycobiology","author":"Pascal Gagneux T. 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