Free urinary sialic acid levels may be elevated in patients with pneumococcal sepsis

Sarah E. Donoghue; Oliver Heath; James Pitt; Kai Mun Hong; Maria Fuller; Joel Smith

doi:10.1515/cclm-2022-0473

Article

Free urinary sialic acid levels may be elevated in patients with pneumococcal sepsis

Sarah E. Donoghue , Oliver Heath , James Pitt , Kai Mun Hong , Maria Fuller and Joel Smith

Published/Copyright: August 25, 2022

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From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 60 Issue 11

Abstract

Objectives

Urine free sialic acid (UFSA) is an important diagnostic biomarker for sialuria (GNE variants) and infantile sialic acid storage disease/Salla disease (SLC17A5 variants). Traditionally, UFSA has been measured using specific single-plex methodology in relatively small cohorts of patients with clinical symptoms suggestive of these disorders. The use of multiplex tandem mass spectrometry urine screening (UMSMS) has meant that UFSA can be measured semi-quantitatively in a much larger cohort of patients being investigated for suspected metabolic disorders. We hypothesised that the neuraminidase of Streptococcus pneumoniae may release free sialic acid from endogenous sialylated glycoconjugates and result in increased UFSA levels.

Methods

We conducted a retrospective review of clinical records of patients who were identified as having S. pneumoniae infection and who also had UMSMS at the time of their acute infection.

Results

We identified three cases of increased UFSA detected by UMSMS screening that were secondary to S. pneumoniae sepsis. Additional testing ruled out genetic causes 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.

Conclusions

We have demonstrated in a retrospective cohort that elevation of UFSA levels have been observed in cases of S. pneumoniae 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.

Keywords: abnormal glycosylation; Streptococcus pneumoniae sepsis; urinary free sialic acid

Corresponding author: Sarah E. Donoghue, Department of Metabolic Medicine, The Royal Children’s Hospital, Melbourne, VIC, Australia; and Department of Biochemical Genetics, Victorian Clinical Genetics Service, Murdoch Children’s Research Institute, Melbourne, VIC, Australia, E-mail: sarah.donoghue@mcri.edu.au

Acknowldgments

We would like to acknowledge the laboratory staff at VCGS and SA Pathology for performing the screening and quantitation of urine free sialic acid levels.

Research funding: None declared.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Informed consent: Not applicable.
Ethical approval: The local Institutional Review Board provided ethics review for this study (ERM:63070).

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Received: 2022-05-24

Accepted: 2022-08-16

Published Online: 2022-08-25

Published in Print: 2022-10-26

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Articles in the same Issue

https://doi.org/10.1515/cclm-2022-0473

Keywords for this article

abnormal glycosylation; Streptococcus pneumoniae sepsis; urinary free sialic acid