{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:55:17Z","timestamp":1790805317235,"version":"4.1.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2012,7,1]],"date-time":"2012-07-01T00:00:00Z","timestamp":1341100800000},"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\/501100010429","name":"Erasmus MC Vriendenfonds","doi-asserted-by":"publisher","award":["1054"],"award-info":[{"award-number":["1054"]}],"id":[{"id":"10.13039\/501100010429","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Consortium for Lysosomal Storage Diseases","award":["F2\/2008"],"award-info":[{"award-number":["F2\/2008"]}]},{"name":"European Consortium for Lysosomal Storage Diseases","award":["201678"],"award-info":[{"award-number":["201678"]}]},{"name":"Dutch Organization for Healthcare Research and Innovation of Care","award":["152001005"],"award-info":[{"award-number":["152001005"]}]},{"name":"Sustainable Orphan Drug Development","award":["T6\u2013208"],"award-info":[{"award-number":["T6\u2013208"]}]},{"DOI":"10.13039\/501100004243","name":"Prinses Beatrix Spierfonds","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004243","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Urinary excretion of the tetrasaccharide 6-\u03b1-D-glucopyranosyl-maltotriose (Glc4) is increased in various clinical conditions associated with increased turnover or storage of glycogen, making Glc4 a potential biomarker for glycogen storage diseases (GSD). We developed an ultraperformance liquid chromatography\u2013tandem mass spectrometry (UPLC-MS\/MS) assay to detect Glc4 in urine without interference of the Glc4 isomer maltotetraose (M4).<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Urine samples, diluted in 0.1% ammonium hydroxide containing the internal standard acarbose, were filtered, and the filtrate was analyzed by UPLC-MS\/MS.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>We separated and quantified acarbose, M4, and Glc4 using the ion pairs m\/z 644\/161, 665\/161, and 665\/179, respectively. Response of Glc4 was linear up to 1500 \u03bcmol\/L and the limit of quantification was 2.8 \u03bcmol\/L. Intra- and interassay CVs were 18.0% and 18.4% (10 \u03bcmol\/L Glc4), and 10.5% and 16.2% (200 \u03bcmol\/L Glc4). Glc4 in control individuals (n = 116) decreased with increasing age from a mean value of 8.9 mmol\/mol to 1.0 mmol\/mol creatinine. M4 was present in 5% of urine samples. Mean Glc4 concentrations per age group in untreated patients with Pompe disease (GSD type II) (n = 66) were significantly higher, ranging from 39.4 to 10.3 mmol\/mol creatinine (P &amp;lt; 0.001\u20130.005). The diagnostic sensitivity of Glc4 for GSD-II was 98.5% and the diagnostic specificity 92%. Urine Glc4 was also increased in GSD-III (8 of 9), GSD-IV (2 of 3) and GSD-IX (6 of 10) patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>The UPLC-MS\/MS assay of Glc4 in urine was discriminative between Glc4 and M4 and confirmed the diagnosis in &amp;gt;98% of GSD-II cases.<\/jats:p><\/jats:sec>","DOI":"10.1373\/clinchem.2011.178319","type":"journal-article","created":{"date-parts":[[2012,5,24]],"date-time":"2012-05-24T03:08:14Z","timestamp":1337828894000},"page":"1139-1147","source":"Crossref","is-referenced-by-count":43,"title":["Rapid Ultraperformance Liquid Chromatography\u2013Tandem Mass Spectrometry Assay for a Characteristic Glycogen-Derived Tetrasaccharide in Pompe Disease and Other Glycogen Storage Diseases"],"prefix":"10.1093","volume":"58","author":[{"given":"Wim","family":"Sluiter","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen C","family":"van den Bosch","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daphne A","family":"Goudriaan","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carin M","family":"van Gelder","sequence":"first","affiliation":[{"name":"Department of Pediatrics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juna M","family":"de Vries","sequence":"first","affiliation":[{"name":"Department of Neurology, Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan G M","family":"Huijmans","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnold J J","family":"Reuser","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ans T","family":"van der Ploeg","sequence":"first","affiliation":[{"name":"Department of Pediatrics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George J G","family":"Ruijter","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,7,1]]},"reference":[{"key":"2020022705121942200_B1","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1111\/j.1365-2362.1974.tb02358.x","article-title":"Increased excretion of a glucose-containing tetrasaccharide in the urine of a patient with glycogen storage disease type II (Pompe's disease)","volume":"4","author":"Hallgren","year":"1974","journal-title":"Eur J Clin Invest"},{"key":"2020022705121942200_B2","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1016\/S0140-6736(83)92122-0","article-title":"Increased urinary excretion of a glycogen-derived tetrasaccharide in heterozygotes with glycogen storage diseases type II and III","volume":"1","author":"Chester","year":"1983","journal-title":"Lancet"},{"key":"2020022705121942200_B3","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1093\/clinchem\/36.7.1381a","article-title":"Unique oligosaccharide (apparently glucotetrasaccharide) in urine of patients with glycogen storage diseases","volume":"36","author":"Oberholzer","year":"1990","journal-title":"Clin Chem"},{"key":"2020022705121942200_B4","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/0014-5793(79)80095-2","article-title":"Increased urinary excretion of a glucose-containing tetrasaccharide in patients with Duchenne muscular dystrophy","volume":"97","author":"Lundblad","year":"1979","journal-title":"FEBS Lett"},{"key":"2020022705121942200_B5","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1016\/S0021-9258(19)75202-8","article-title":"Quantitation of some urinary oligosaccharides during pregnancy and lactation","volume":"252","author":"Hallgren","year":"1977","journal-title":"J Biol Chem"},{"key":"2020022705121942200_B6","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1002\/bms.1200030202","article-title":"Quantitation of a urinary tetrasaccharide by gas chromatography and mass spectrometry","volume":"3","author":"Lennartson","year":"1976","journal-title":"Biomed Mass Spectrom"},{"key":"2020022705121942200_B7","first-page":"27","article-title":"Studies on the metabolic origin of a glucose-containing tetrasaccharide in human urine","volume":"1","author":"Ugorski","year":"1983","journal-title":"J Exp Pathol"},{"key":"2020022705121942200_B8","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1006\/abio.2000.4838","article-title":"Liquid chromatographic assay for a glucose tetrasaccharide, a putative biomarker for the diagnosis of Pompe disease","volume":"287","author":"An","year":"2000","journal-title":"Anal Biochem"},{"key":"2020022705121942200_B9","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S0003-2697(03)00056-3","article-title":"Analysis of a glucose tetrasaccharide elevated in Pompe disease by stable isotope dilution-electrospray ionization tandem mass spectrometry","volume":"316","author":"Young","year":"2003","journal-title":"Anal Biochem"},{"key":"2020022705121942200_B10","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1038\/sj.ejhg.5200367","article-title":"Frequency of glycogen storage disease type II in The Netherlands: implications for diagnosis and genetic counseling","volume":"7","author":"Ausems","year":"1999","journal-title":"Eur J Hum Genet"},{"key":"2020022705121942200_B11","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1016\/S0140-6736(08)61555-X","article-title":"Pompe's disease","volume":"372","author":"van der Ploeg","year":"2008","journal-title":"Lancet"},{"key":"2020022705121942200_B12","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/S0140-6736(00)02533-2","article-title":"Recombinant human alpha-glucosidase from rabbit milk in Pompe patients","volume":"356","author":"van den Hout","year":"2000","journal-title":"Lancet"},{"key":"2020022705121942200_B13","first-page":"132","article-title":"Recombinant human acid alpha-glucosidase enzyme therapy for infantile glycogen storage disease type II: results of a phase I\/II clinical trial","volume":"3","author":"Amalfitano","year":"2001","journal-title":"Genet Med"},{"key":"2020022705121942200_B14","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1097\/GIM.0b013e3181a87867","article-title":"Long-term monitoring of patients with infantile-onset Pompe disease on enzyme replacement therapy using a urinary glucose tetrasaccharide biomarker","volume":"11","author":"Young","year":"2009","journal-title":"Genet Med"},{"key":"2020022705121942200_B15","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1002\/ajmg.c.31320","article-title":"Assessing disease severity in Pompe disease: the roles of a urinary glucose tetrasaccharide biomarker and imaging techniques","volume":"160","author":"Young","year":"2012","journal-title":"Am J Med Genet C Semin Med Genet"},{"key":"2020022705121942200_B16","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/0009-8981(83)90200-0","article-title":"Thin-layer chromatography of oligosaccharides in urine as a rapid indication for the diagnosis of lysosomal acid maltase deficiency (Pompe's disease)","volume":"134","author":"Blom","year":"1983","journal-title":"Clin Chim Acta"},{"key":"2020022705121942200_B17","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/s10545-011-9360-2","article-title":"Urine analysis of glucose tetrasaccharide by HPLC; a useful marker for the investigation of patients with Pompe and other glycogen storage diseases","volume":"35","author":"Manwaring","year":"2011","journal-title":"J Inherit Metab Dis"},{"key":"2020022705121942200_B18","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1093\/clinchem\/48.1.131","article-title":"Determination of oligosaccharides in Pompe disease by electrospray ionization tandem mass spectrometry","volume":"48","author":"Rozaklis","year":"2002","journal-title":"Clin Chem"},{"key":"2020022705121942200_B19","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1373\/49.7.1041","article-title":"Ion suppression in mass spectrometry","volume":"49","author":"Annesley","year":"2003","journal-title":"Clin Chem"},{"key":"2020022705121942200_B20","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1093\/jn\/137.3.847S","article-title":"Oligosaccharides from milk","volume":"137","author":"Boehm","year":"2007","journal-title":"J Nutr"},{"key":"2020022705121942200_B21","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/0009-8981(88)90172-6","article-title":"Urinary excretion of a glucose-containing tetrasaccharide. A parameter for increased degradation of glycogen","volume":"176","author":"Kumlien","year":"1988","journal-title":"Clin Chim Acta"},{"key":"2020022705121942200_B22","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.ymgme.2007.06.007","article-title":"Glycogen storage disease type IX: high variability in clinical phenotype","volume":"92","author":"Beauchamp","year":"2007","journal-title":"Mol Genet Metab"},{"key":"2020022705121942200_B23","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.nmd.2009.11.004","article-title":"Muscle phosphorylase b kinase deficiency revisited","volume":"20","author":"Echaniz-Laguna","year":"2010","journal-title":"Neuromuscul Disord"},{"key":"2020022705121942200_B24","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1517\/17530050903460300","article-title":"Enzymatic and molecular strategies to diagnose Pompe disease","volume":"4","author":"Reuser","year":"2010","journal-title":"Exp Opin Med Diagn"},{"key":"2020022705121942200_B25","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.ymgme.2005.03.010","article-title":"Glucose tetrasaccharide as a biomarker for monitoring the therapeutic response to enzyme replacement therapy for Pompe disease","volume":"85","author":"An","year":"2005","journal-title":"Mol Genet Metab"}],"container-title":["Clinical Chemistry"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/clinchem\/article-pdf\/58\/7\/1139\/32657890\/clinchem1139.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/clinchem\/article-pdf\/58\/7\/1139\/32657890\/clinchem1139.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,16]],"date-time":"2022-01-16T05:13:46Z","timestamp":1642310026000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/clinchem\/article\/58\/7\/1139\/5620781"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,7,1]]},"references-count":25,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2012,7,1]]},"published-print":{"date-parts":[[2012,7,1]]}},"URL":"https:\/\/doi.org\/10.1373\/clinchem.2011.178319","relation":{},"ISSN":["0009-9147","1530-8561"],"issn-type":[{"value":"0009-9147","type":"print"},{"value":"1530-8561","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2012,7,1]]},"published":{"date-parts":[[2012,7,1]]}}}