A New UHPLC-MS/MS Method for the Screening of Urinary Oligosaccharides Expands the Detection of Storage Disorders

Overview

Journal Orphanet J Rare Dis

Publisher Biomed Central

Specialty General Medicine

Date 2021 Jan 10

PMID 33422100

Citations 3

Authors

Michela Semeraro

Elisa Sacchetti

Federica Deodato

Turgay Coskun

Incilay Lay

Giulio Catesini

Giorgia Olivieri

Cristiano Rizzo

Sara Boenzi

Carlo Dionisi-Vici

Affiliations

Soon will be listed here.

Abstract

Background: Oligosaccharidoses are storage disorders due to enzymatic defects involved in the breakdown of the oligosaccharidic component of glycosylated proteins. The defect cause the accumulation of oligosaccharides (OS) and, depending on the lacking enzyme, results in characteristic profiles which are helpful for the diagnosis. We developed a new tandem mass spectrometry method for the screening of urinary OS which was applied to identify a large panel of storage disorders.

Methods: The method was set-up in urine and dried urine spots (DUS). Samples were analysed, without derivatization and using maltoheptaose as internal standard, by UHPLC-MS/MS with MRM acquisition of target OS transitions, including Glc4, the biomarker of Pompe disease. The chromatographic run was < 30 min. Samples from patients with known storage disorders were used for clinical validation.

Results: The method allowed to confirm the diagnosis of oligosaccharidoses (sialidosis, α-/β-mannosidosis, fucosidosis, aspartylglucosaminuria) and of GM1 and GM2 (Sandhoff type) gangliosidosis, by detecting specific OS profiles. In other storage disorders (mucolipidosis II and III, mucopolysaccharidosis type IVB) the analyisis revealed abnormal OS excretion with non-specific profiles. Besides Pompe disease, the tetrasaccharide Glc4 was increased also in disorders of autophagy (Vici syndrome, Yunis-Varon syndrome, and Danon disease) presenting cardiomuscular involvement with glycogen storage. Overall, results showed a clear separation between patients and controls, both in urine and in DUS.

Conclusion: This new UHPLC/MS-MS method, which is suitable for rapid and easy screening of OS in urine and DUS, expands the detection of storage disorders from oligosaccharidoses to other diseases, including the novel category of inherited disorders of autophagy.

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References

Ferreira C, Gahl W . Lysosomal storage diseases. Transl Sci Rare Dis. 2017; 2(1-2):1-71. PMC: 5685203. DOI: 10.3233/TRD-160005. View

Bonesso L, Piraud M, Caruba C, Van Obberghen E, Mengual R, Hinault C . Fast urinary screening of oligosaccharidoses by MALDI-TOF/TOF mass spectrometry. Orphanet J Rare Dis. 2014; 9:19. PMC: 3922009. DOI: 10.1186/1750-1172-9-19. View

Garcia-Cazorla A, Saudubray J . Cellular neurometabolism: a tentative to connect cell biology and metabolism in neurology. J Inherit Metab Dis. 2018; 41(6):1043-1054. PMC: 6326994. DOI: 10.1007/s10545-018-0226-8. View

Byrne S, Dionisi-Vici C, Smith L, Gautel M, Jungbluth H . Vici syndrome: a review. Orphanet J Rare Dis. 2016; 11:21. PMC: 4772338. DOI: 10.1186/s13023-016-0399-x. View

Cullup T, Kho A, Dionisi-Vici C, Brandmeier B, Smith F, Urry Z . Recessive mutations in EPG5 cause Vici syndrome, a multisystem disorder with defective autophagy. Nat Genet. 2012; 45(1):83-7. PMC: 4012842. DOI: 10.1038/ng.2497. View

Bruggink C, Poorthuis B, Deelder A, Wuhrer M . Analysis of urinary oligosaccharides in lysosomal storage disorders by capillary high-performance anion-exchange chromatography-mass spectrometry. Anal Bioanal Chem. 2012; 403(6):1671-83. PMC: 3354319. DOI: 10.1007/s00216-012-5968-9. View

Dworzak F, Mora M, Borroni C, Cornelio F, Blasevich F, Cappellini A . Generalized lysosomal storage in Yunis Varón syndrome. Neuromuscul Disord. 1995; 5(5):423-8. DOI: 10.1016/0960-8966(94)00089-r. View

Young S, Piraud M, Goldstein J, Zhang H, Rehder C, Laforet P . Assessing disease severity in Pompe disease: the roles of a urinary glucose tetrasaccharide biomarker and imaging techniques. Am J Med Genet C Semin Med Genet. 2012; 160C(1):50-8. DOI: 10.1002/ajmg.c.31320. View

Humbel R, Collart M . Oligosaccharides in urine of patients with glycoprotein storage diseases. I. Rapid detection by thin-layer chromatography. Clin Chim Acta. 1975; 60(2):143-5. DOI: 10.1016/0009-8981(75)90119-9. View

10.

Ramsay S, Maire I, Bindloss C, Fuller M, Whitfield P, Piraud M . Determination of oligosaccharides and glycolipids in amniotic fluid by electrospray ionisation tandem mass spectrometry: in utero indicators of lysosomal storage diseases. Mol Genet Metab. 2004; 83(3):231-8. DOI: 10.1016/j.ymgme.2004.07.015. View

11.

Ramsay S, Meikle P, Hopwood J, Clements P . Profiling oligosaccharidurias by electrospray tandem mass spectrometry: quantifying reducing oligosaccharides. Anal Biochem. 2005; 345(1):30-46. DOI: 10.1016/j.ab.2005.06.042. View

12.

Levine B, Kroemer G . Biological Functions of Autophagy Genes: A Disease Perspective. Cell. 2019; 176(1-2):11-42. PMC: 6347410. DOI: 10.1016/j.cell.2018.09.048. View

13.

Farah B, Yen P, Koeberl D . Links between autophagy and disorders of glycogen metabolism - Perspectives on pathogenesis and possible treatments. Mol Genet Metab. 2019; 129(1):3-12. PMC: 7836271. DOI: 10.1016/j.ymgme.2019.11.005. View

14.

Canbay E, Vural M, Ucar S, Sezer E, Karasoy H, Yuceyar A . The decision-making levels of urine tetrasaccharide for the diagnosis of Pompe disease in the Turkish population. J Pediatr Endocrinol Metab. 2020; 33(3):391-395. DOI: 10.1515/jpem-2019-0393. View

15.

Mashima R, Okuyama T, Ohira M . Biomarkers for Lysosomal Storage Disorders with an Emphasis on Mass Spectrometry. Int J Mol Sci. 2020; 21(8). PMC: 7215887. DOI: 10.3390/ijms21082704. View

16.

Ferreira C, van Karnebeek C, Vockley J, Blau N . A proposed nosology of inborn errors of metabolism. Genet Med. 2018; 21(1):102-106. PMC: 6286709. DOI: 10.1038/s41436-018-0022-8. View

17.

Kurczynski T, Kendzierski K, Sewell A, Kuczynski T . Urinary oligosaccharides in pregnant or lactating women: pitfall in screening. Clin Chem. 1993; 39(11 Pt 1):2346-7. View

18.

Veinot J, Nair V . Lysosomal storage disorders affecting the heart: a review. Cardiovasc Pathol. 2020; 48:107217. DOI: 10.1016/j.carpath.2020.107217. View

19.

Walch E, Schmidt M, Brenner R, Emons D, Dame C, Pontz B . Yunis-Varon syndrome: evidence for a lysosomal storage disease. Am J Med Genet. 2000; 95(2):157-60. DOI: 10.1002/1096-8628(20001113)95:2<157::aid-ajmg12>3.0.co;2-e. View

20.

Sluiter W, van den Bosch J, Goudriaan D, Van Gelder C, de Vries J, Huijmans J . Rapid ultraperformance liquid chromatography-tandem mass spectrometry assay for a characteristic glycogen-derived tetrasaccharide in Pompe disease and other glycogen storage diseases. Clin Chem. 2012; 58(7):1139-47. DOI: 10.1373/clinchem.2011.178319. View