Accessible Requires Authentication Published by De Gruyter February 18, 2020

The decision-making levels of urine tetrasaccharide for the diagnosis of Pompe disease in the Turkish population

Erhan Canbay, Melisa Vural, Sema Kalkan Uçar, Ebru Demirel Sezer, Hatice Karasoy, Ayşe Nur Yüceyar, Mahmut Çoker and Eser Yildirim Sözmen

Abstract

Background

Recently, urinary excretion of the tetrasaccharide 6-α-D-glucopyranosyl-maltotriose (Glc4) has been proposed as a marker for the diagnosis and monitoring of Pompe disease (PD). We aimed to determine the reference intervals and reliable decision-making levels of urine tetrasaccharide concentrations for the diagnosis of infantile- and late-onset Pompe patients in the Turkish population.

Methods

In this study, nine patients with PD (five of them with late-onset PD [LOPD]) and 226 healthy individuals (aged 0–64 years) were included. Urine Glc4 concentrations were determined using the ultra-high-performance liquid chromatography (UHPLC) tandem mass spectrometry (MS/MS) method.

Results

Our data showed that the urine tetrasaccharide levels decreased with age in healthy individuals (p < 0.001, r = −0.256). It was higher especially during the first year of life compared to that in the elder subjects. The tetrasaccharide level of Pompe patients was higher compared to that of healthy controls of the same age: 99 ± 68 mmol/mol creatinine for infantile onset vs. 4.0 ± 3.0 mmol/mol creatinine for healthy controls of the same age group and 12.1 ± 17.4 mmol/mol creatinine for late onset vs. 1.7±1.2 mmol/mol creatinine for healthy controls of the same age group.

Conclusions

The results of this study showed that the reference intervals of tetrasaccharide in urine changed over time; therefore, it is critically important to define age-based decision levels for the diagnosis of LOPD.


Corresponding author: Prof. Eser Yildirim Sözmen, MD, PhD, Ege University, Faculty of Medicine, Department of Medical Biochemistry, Izmir, Turkey, Phone: +90 232 3904098, Fax: +90 232 3904030

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) does not have a role in the design of the study; in the collection, analysis, and interpretation of data; in writing the report; nor in the decision to submit the report for publication.

References

1. Kemper AR, Hwu WL, Lloyd-Puryear M, Kishnani PS. Newborn screening for Pompe disease: synthesis of the evidence and development of screening recommendations. Pediatrics 2007;120:1327–34. Search in Google Scholar

2. ACMG Work Group on Management of Pompe Disease, Kishnani PS, Steiner RD, Bali D, Berger K, et al. Pompe disease diagnosis and management guideline. Genet Med 2006;8:267–88. Search in Google Scholar

3. Spada M, Pagliardini M, Ricci F, Biamino E, Mongini T, et al. Early higher dosage of alglucosidase alpha in classic Pompe disease. J Pediatr Endocrinol Metab 2018;31:1343–7. Search in Google Scholar

4. Chien YH, Goldstein JL, Hwu WL, Smith PB, Lee NC, et al. Baseline urinary glucose tetrasaccharide concentrations in patients with infantile- and late-onset Pompe disease identified by newborn screening. JIMD Rep 2015;19:67–73. Search in Google Scholar

5. Kumlien J, Chester MA, Lindberg BS, Pizzo P, Zopf D, et al. Urinary excretion of a glucose-containing tetrasaccharide. A parameter for increased degradation of glycogen. Clin Chim Acta 1988;176:39–48. Search in Google Scholar

6. Young SP, Zhang H, Corzo D, Thurberg BL, Bali D, et al. Long-term monitoring of patients with infantile-onset Pompe disease on enzyme replacement therapy using a urinary glucose tetrasaccharide biomarker. Genet Med 2009;11:536–41. Search in Google Scholar

7. Young SP, Piraud M, Goldstein JL, Zhang H, Rehder C, et al. 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:50–8. Search in Google Scholar

8. Young SP, Stevens RD, An Y, Chen Y-T, Millington DS. Analysis of a glucose tetrasaccharide elevated in Pompe disease by stable isotope dilution–electrospray ionization tandem mass spectrometry. Anal Biochem 2003;316:175–80. Search in Google Scholar

9. Ann Y, Young SP, Kishnani PS, Millington DS, Wtano AA, et al. Glucose tetrasaccharide as a biomarker for monitoring the therapeutic response to enzyme replacement therapy for Pompe disease. Mol Genet Metab 2005;85:247–54. Search in Google Scholar

10. Blom W, Luteyn JC, Kelholt-Dijkman HH, Huijmans JG, LoonenMC. Thin-layer chromatography of oligosaccharides in urine as a rapid indication for the diagnosis of lysosomal acid maltase deficiency (Pompe’s disease). Clin Chim Acta 1983;134:221–7. Search in Google Scholar

11. An Y, Young SP, Hillman SL, Van Hove LK, Chen YT, et al. Liquid chromatographic assay for a glucose tetrasaccharide, a putative biomarker for the diagnosis of Pompe disease. Anal Biochem 2000;287:136–43. Search in Google Scholar

12. Sluiter W, van den Bosch JC, Goudriaan DA, van Gelder CM, de Vries JM, et al. 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;58:1139–47. Search in Google Scholar

13. National Committee for Clinical Laboratory Standards. How to define and determine reference intervals in the clinical laboratory: approved guideline. 2001, NCCLS document C28-A and C28-A2, Villanova, PA, NCCLS. Search in Google Scholar

14. Horn PS, Pesce AJ. Reference intervals: an update. Clin Chim Acta 2003;334:5–23. Search in Google Scholar

15. Aldemir O, Ergun P, Güneş S, Köroğlu OA, Yalaz M, et al. Reference intervals of α-glycosidase, β-glycosidase and α-galactosidase ın drıed blood spot of newborn ın a Turkish population. Eur J Pediatrics 2013;172:1221–7. Search in Google Scholar

Received: 2019-08-24
Accepted: 2020-01-06
Published Online: 2020-02-18
Published in Print: 2020-03-26

©2020 Walter de Gruyter GmbH, Berlin/Boston