{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T04:56:53Z","timestamp":1785214613867,"version":"3.55.0"},"reference-count":22,"publisher":"Walter de Gruyter GmbH","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,10,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec id=\"j_cclm-2022-0473_abs_001\">\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Urine free sialic acid (UFSA) is an important diagnostic biomarker for sialuria (<jats:italic>GNE<\/jats:italic> variants) and infantile sialic acid storage disease\/Salla disease (<jats:italic>SLC17A5<\/jats:italic> variants). Traditionally, UFSA has been measured using specific single-plex methodology in relatively small cohorts of patients with clinical symptoms suggestive of\u00a0these disorders. The use of multiplex tandem mass spectrometry urine screening (UMSMS) has meant that UFSA can be measured semi-quantitatively in a much\u00a0larger cohort of patients being investigated for suspected metabolic disorders. We hypothesised that the\u00a0neuraminidase of <jats:italic>Streptococcus pneumoniae<\/jats:italic> may release free sialic acid from endogenous sialylated glycoconjugates and result in\u00a0increased UFSA levels.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_cclm-2022-0473_abs_002\">\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted a retrospective review of clinical records of patients who were identified as having <jats:italic>S.\u00a0pneumoniae<\/jats:italic> infection and who also had UMSMS at the time\u00a0of their acute infection.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_cclm-2022-0473_abs_003\">\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We identified three cases of increased UFSA detected by UMSMS screening that were secondary to <jats:italic>S.\u00a0pneumoniae<\/jats:italic> sepsis. Additional testing ruled out genetic\u00a0causes of increased UFSA in the first patient. All three patients had overwhelming sepsis with multiorgan dysfunction which was fatal. Glycosylation abnormalities consistent with the removal of sialic acid were demonstrated in serum transferrin patterns in one patient.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_cclm-2022-0473_abs_004\">\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>We have demonstrated in a retrospective cohort that elevation of UFSA levels have been observed in\u00a0cases of <jats:italic>S.\u00a0pneumoniae<\/jats:italic> sepsis. This expands our knowledge of UFSA as a biomarker in human disease. This research demonstrates that infection with organisms with neuraminidase activity should be considered in patients with unexplained increases in UFSA.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1515\/cclm-2022-0473","type":"journal-article","created":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T09:32:35Z","timestamp":1661333555000},"page":"1855-1858","source":"Crossref","is-referenced-by-count":2,"title":["Free urinary sialic acid levels may be elevated in patients with pneumococcal sepsis"],"prefix":"10.1515","volume":"60","author":[{"given":"Sarah E.","family":"Donoghue","sequence":"first","affiliation":[{"name":"Department of Metabolic Medicine , The Royal Children\u2019s Hospital , Melbourne , VIC , Australia"},{"name":"Department of Biochemical Genetics , Victorian Clinical Genetics Service, Murdoch Children\u2019s Research Institute , Melbourne , VIC , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Heath","sequence":"additional","affiliation":[{"name":"Department of Metabolic Medicine , The Royal Children\u2019s Hospital , Melbourne , VIC , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Pitt","sequence":"additional","affiliation":[{"name":"Department of Biochemical Genetics , Victorian Clinical Genetics Service, Murdoch Children\u2019s Research Institute , Melbourne , VIC , Australia"},{"name":"Department of Paediatrics , University of Melbourne , Melbourne , VIC , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai Mun","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Biochemical Genetics , Victorian Clinical Genetics Service, Murdoch Children\u2019s Research Institute , Melbourne , VIC , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Fuller","sequence":"additional","affiliation":[{"name":"Genetics and Molecular Pathology , SA Pathology , Adelaide , SA , Australia"},{"name":"Adelaide Medical School, University of Adelaide , Adelaide , SA , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Smith","sequence":"additional","affiliation":[{"name":"Laboratory Services , Royal Children\u2019s Hospital , Melbourne , VIC , Australia"},{"name":"Department of Pathology , Royal Melbourne Hospital , Melbourne , VIC , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2022,8,25]]},"reference":[{"key":"2023033113340218743_j_cclm-2022-0473_ref_001","doi-asserted-by":"crossref","unstructured":"Varki, A. 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