{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T23:58:09Z","timestamp":1792195089847,"version":"4.4.0"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T00:00:00Z","timestamp":1556668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Congenital disorders of glycosylation (CDG) represent 1 of the largest groups of metabolic disorders with &amp;gt;130 subtypes identified to date. The majority of CDG subtypes are disorders of N-linked glycosylation, in which carbohydrate residues, namely, N-glycans, are posttranslationally linked to asparagine molecules in peptides. To improve the diagnostic capability for CDG, we developed and validated a plasma N-glycan assay using flow injection\u2013electrospray ionization\u2013quadrupole time-of-flight mass spectrometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>After PNGase F digestion of plasma glycoproteins, N-glycans were linked to a quinolone using a transient amine group at the reducing end, isolated by a hydrophilic interaction chromatography column, and then identified by accurate mass and quantified using a stable isotope-labeled glycopeptide as the internal standard.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>This assay differed from other N-glycan profiling methods because it was free of any contamination from circulating free glycans and was semiquantitative. The low end of the detection range tested was at 63 nmol\/L for disialo-biantennary N-glycan. The majority of N-glycans in normal plasma had &amp;lt;1% abundance. Abnormal N-glycan profiles from 19 patients with known diagnoses of 11 different CDG subtypes were generated, some of which had previously been reported to have normal N-linked protein glycosylation by carbohydrate-deficient transferrin analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>The clinical specificity and sensitivity of N-glycan analysis was much improved with this method. Additional CDGs can be diagnosed that would be missed by carbohydrate-deficient transferrin analysis. The assay provides novel biomarkers with diagnostic and potentially therapeutic significance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1373\/clinchem.2018.296780","type":"journal-article","created":{"date-parts":[[2019,2,15]],"date-time":"2019-02-15T17:45:14Z","timestamp":1550252714000},"page":"653-663","source":"Crossref","is-referenced-by-count":64,"title":["Increased Clinical Sensitivity and Specificity of Plasma Protein N-Glycan Profiling for Diagnosing Congenital Disorders of Glycosylation by Use of Flow Injection\u2013Electrospray Ionization\u2013Quadrupole Time-of-Flight Mass Spectrometry"],"prefix":"10.1093","volume":"65","author":[{"given":"Jie","family":"Chen","sequence":"first","affiliation":[{"name":"Division of Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueli","family":"Li","sequence":"first","affiliation":[{"name":"Division of Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Edmondson","sequence":"first","affiliation":[{"name":"Division of Human Genetics, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gail Ditewig","family":"Meyers","sequence":"first","affiliation":[{"name":"Division of Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosuke","family":"Izumi","sequence":"first","affiliation":[{"name":"Division of Human Genetics, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda M","family":"Ackermann","sequence":"first","affiliation":[{"name":"Division of Endocrinology and Diabetes, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Morava","sequence":"first","affiliation":[{"name":"Department of Clinical Genomics, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Ficicioglu","sequence":"first","affiliation":[{"name":"Division of Human Genetics, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J","family":"Bennett","sequence":"first","affiliation":[{"name":"Division of Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA"},{"name":"Department of Pathology and Laboratory Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"He","sequence":"first","affiliation":[{"name":"Division of Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA"},{"name":"Department of Pathology and Laboratory Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,5,1]]},"reference":[{"key":"2020022605530692900_B1","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.tig.2018.03.002","article-title":"Perspectives on glycosylation and its congenital disorders","volume":"34","author":"Ng","year":"2018","journal-title":"Trends Genet"},{"key":"2020022605530692900_B2","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/j.ejmg.2017.10.012","article-title":"Congenital disorders of glycosylation (CDG): quo vadis?","volume":"61","author":"Peanne","year":"2018","journal-title":"Eur J Med Genet"},{"key":"2020022605530692900_B3","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1007\/s10719-015-9639-x","article-title":"Clinical diagnostics and therapy monitoring in the congenital disorders of glycosylation","volume":"33","author":"Van Scherpenzeel","year":"2016","journal-title":"Glycoconj J"},{"key":"2020022605530692900_B4","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.ab.2013.07.037","article-title":"Serum N-glycan and O-glycan analysis by mass spectrometry for diagnosis of congenital disorders of glycosylation","volume":"442","author":"Xia","year":"2013","journal-title":"Anal Biochem"},{"key":"2020022605530692900_B5","doi-asserted-by":"crossref","first-page":"4402","DOI":"10.1021\/acs.jproteome.5b00709","article-title":"N-Glycosylation of serum IgG and total glycoproteins in MAN1B1 deficiency","volume":"14","author":"Saldova","year":"2015","journal-title":"J Proteome Res"},{"key":"2020022605530692900_B6","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1373\/clinchem.2015.243279","article-title":"A novel N-tetrasaccharide in patients with congenital disorders of glycosylation, including asparagine-linked glycosylation protein 1, phosphomannomutase 2, and mannose phosphate isomerase deficiencies","volume":"62","author":"Zhang","year":"2016","journal-title":"Clin Chem"},{"key":"2020022605530692900_B7","doi-asserted-by":"crossref","first-page":"5401","DOI":"10.1021\/acs.analchem.5b00758","article-title":"Rapid preparation of released N-glycans for HILIC analysis using a labeling reagent that facilitates sensitive fluorescence and ESI-MS detection","volume":"87","author":"Lauber","year":"2015","journal-title":"Anal Chem"},{"key":"2020022605530692900_B8","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1002\/humu.22983","article-title":"ALG1-CDG: clinical and molecular characterization of 39 unreported patients","volume":"37","author":"Ng","year":"2016","journal-title":"Hum Mutat"},{"key":"2020022605530692900_B9","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.ymgmr.2017.08.004","article-title":"ALG9-CDG: new clinical case and review of the literature","volume":"13","author":"Davis","year":"2017","journal-title":"Mol Genet Metab Rep"},{"key":"2020022605530692900_B10","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1038\/gim.2017.41","article-title":"Oral D-galactose supplementation in PGM1-CDG","volume":"19","author":"Wong","year":"2017","journal-title":"Genet Med"},{"key":"2020022605530692900_B11","doi-asserted-by":"crossref","first-page":"3050","DOI":"10.1093\/hmg\/ddv057","article-title":"Biallelic mutations in CAD, impair de novo pyrimidine biosynthesis, and decrease glycosylation precursors","volume":"24","author":"Ng","year":"2015","journal-title":"Hum Mol Genet"},{"key":"2020022605530692900_B12","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.ajhg.2016.06.011","article-title":"ARCN1 mutations cause a recognizable craniofacial syndrome due to COPI-mediated transport defects","volume":"99","author":"Izumi","year":"2016","journal-title":"Am J Hum Genet"},{"key":"2020022605530692900_B13","unstructured":"Consortium for functional glycomic. CFG data. http:\/\/www.functionalglycomics.org\/glycomics\/publicdata\/home.jsp (Accessed January 2017)."},{"key":"2020022605530692900_B14","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1007\/s10545-017-0050-6","article-title":"What is new in CDG?","volume":"40","author":"Jaeken","year":"2017","journal-title":"J Inherit Metab Dis"},{"key":"2020022605530692900_B15","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.ajhg.2011.12.024","article-title":"DDOST mutations identified by whole-exome sequencing are implicated in congenital disorders of glycosylation","volume":"90","author":"Jones","year":"2012","journal-title":"Am J Hum Genet"},{"key":"2020022605530692900_B16","doi-asserted-by":"crossref","first-page":"4638","DOI":"10.1093\/hmg\/ddt312","article-title":"Mutations in STT3A and STT3B cause two congenital disorders of glycosylation","volume":"22","author":"Shrimal","year":"2013","journal-title":"Hum Mol Genet"},{"key":"2020022605530692900_B17","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.ymgmr.2017.07.010","article-title":"Limitations of galactose therapy in phosphoglucomutase 1 deficiency","volume":"13","author":"Nolting","year":"2017","journal-title":"Mol Genet Metab Rep"},{"key":"2020022605530692900_B18","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.ajhg.2013.03.012","article-title":"Mosaicism of the UDP-galactose transporter SLC35A2 causes a congenital disorder of glycosylation","volume":"92","author":"Ng","year":"2013","journal-title":"Am J Hum Genet"},{"key":"2020022605530692900_B19","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1002\/humu.22446","article-title":"De novo mutations in SLC35A2 encoding a UDP-galactose transporter cause early-onset epileptic encephalopathy","volume":"34","author":"Kodera","year":"2013","journal-title":"Hum Mutat"},{"key":"2020022605530692900_B20","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1007\/s10545-015-9828-6","article-title":"A new case of UDP-galactose transporter deficiency (SLC35A2-CDG): molecular basis, clinical phenotype, and therapeutic approach","volume":"38","author":"Dorre","year":"2015","journal-title":"J Inherit Metab Dis"},{"key":"2020022605530692900_B21","doi-asserted-by":"crossref","first-page":"15475","DOI":"10.1074\/jbc.M115.636670","article-title":"UDP-galactose (SLC35A2) and UDP-N-acetylglucosamine (SLC35A3) transporters form glycosylation-related complexes with mannoside acetylglucosaminyltransferases (Mgats)","volume":"290","author":"Maszczak-Seneczko","year":"2015","journal-title":"J Biol Chem"},{"key":"2020022605530692900_B22","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.ymgme.2012.05.025","article-title":"N- and O-linked glycosylation of total plasma glycoproteins in galactosemia","volume":"106","author":"Liu","year":"2012","journal-title":"Mol Genet Metab"},{"key":"2020022605530692900_B23","doi-asserted-by":"crossref","first-page":"e18959","DOI":"10.1371\/journal.pone.0018959","article-title":"O-GlcNAc-specific antibody CTD110.6 cross-reacts with N-GlcNAc2-modified proteins induced under glucose deprivation","volume":"6","author":"Isono","year":"2011","journal-title":"PLoS One"},{"key":"2020022605530692900_B24","doi-asserted-by":"crossref","first-page":"e96168","DOI":"10.1371\/journal.pone.0096168","article-title":"Glucose deprivation induces G2\/M transition-arrest and cell death in N-GlcNAc2-modified protein-producing renal carcinoma cells","volume":"9","author":"Isono","year":"2014","journal-title":"PLoS One"},{"key":"2020022605530692900_B25","doi-asserted-by":"crossref","first-page":"28207","DOI":"10.1038\/srep28207","article-title":"IgG1 Fc N-glycan galactosylation as a biomarker for immune activation","volume":"6","author":"de Jong","year":"2016","journal-title":"Sci Rep"},{"key":"2020022605530692900_B26","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1111\/liv.13362","article-title":"Impaired N-linked glycosylation of uptake and efflux transporters in human non-alcoholic fatty liver disease","volume":"37","author":"Clarke","year":"2017","journal-title":"Liver Int"},{"key":"2020022605530692900_B27","first-page":"2390","article-title":"Serum glycoprotein-derived N- and O-linked glycans as cancer biomarkers","volume":"6","author":"Lan","year":"2016","journal-title":"Am J Cancer Res"},{"key":"2020022605530692900_B28","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.it.2006.12.003","article-title":"Statins and the vascular endothelial inflammatory response","volume":"28","author":"Greenwood","year":"2007","journal-title":"Trends Immunol"}],"container-title":["Clinical Chemistry"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/clinchem\/article-pdf\/65\/5\/653\/32638485\/clinchem0653.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/clinchem\/article-pdf\/65\/5\/653\/32638485\/clinchem0653.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,2,26]],"date-time":"2020-02-26T05:58:10Z","timestamp":1582696690000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/clinchem\/article\/65\/5\/653\/5608044"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,1]]},"references-count":28,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2019,5,1]]},"published-print":{"date-parts":[[2019,5,1]]}},"URL":"https:\/\/doi.org\/10.1373\/clinchem.2018.296780","relation":{},"ISSN":["0009-9147","1530-8561"],"issn-type":[{"value":"0009-9147","type":"print"},{"value":"1530-8561","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,5,1]]},"published":{"date-parts":[[2019,5,1]]}}}