Skip to main content
SpringerLink
Log in

Reference intervals of α-glycosidase, β-glycosidase, and α-galactosidase in dried blood spot in a Turkish newborn population

  • Original Article
  • Published:
European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Inherited lysosomal storage diseases (LSDs) are rare, and diagnosis is often delayed for 7–10 years. Since the therapies have become available for a limited number of LSDs, (Fabry, Gaucher, Pompe, and MPS-1), early diagnosis of treatable LSDs can be lifesaving or ameliorating and allows timely treatment before irreversible damage occurs. Recently, the use of dried blood spot test (DBS) for newborn screening of LSDs has been proposed for newborn screening tests. They are noninvasive, sensitive, and specific assays with the further advantage of a fast turnaround time compared to measurement in leukocyte and/or fibroblast culture. We aimed to determine the reference intervals for lysosomal enzyme activities of newborn babies in our population and to investigate the effect of gestational week on enzyme activity. One hundred thirty healthy newborn babies (70 girls, 60 boys) were included into the study. α-Glycosidase, β-glycosidase, and α-galactosidase activities in DBS samples of newborns were determined fluorometrically. Reference intervals were calculated using Dixon's rule and percentiles of 2.5–97.5. Cutoff limits (5 %) for α-glycosidase, β-glycosidase, and α-galactosidase activities were 0.57, 0.92, and 2.18, respectively. α-Galactosidase activity was higher in girls compared to boys (p < 0.05). Interestingly, α-glycosidase and β-glycosidase activities of newborns who were delivered before 38 weeks were significantly lower than those who were delivered at 39–40 weeks.

Conclusion It is of utmost importance to define the reference intervals for lysosomal enzyme activities as well as cutoff limits for newborn babies with regard to gestational age and sex. More studies to clarify the reason for the change in enzyme activity by gestational week will be required.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Chamoles NA, Blanco M, Gaggioli D (2001) Fabry disease: enzymatic diagnosis in dried blood spots on filter paper. Clin Chim Acta 308:195–196

    Article  PubMed  CAS  Google Scholar 

  2. Chamoles NA, Blanco M, Gaggioli D, Casentini C (2002) Gaucher and Niemann–Pick diseases—enzymatic diagnosis in dried blood spots on filter paper: retrospective diagnoses in newborn-screening cards. Clin Chim Acta 317:191–197

    Article  PubMed  CAS  Google Scholar 

  3. Chien YH, Lee NC, Thurberg BL, Chiang SC, Zhang KX, Keutzer J, Huang AC, Wu MH, Huang PH, Tsai FJ, Chen YT, Hwu WL (2009) Pompe disease in infants: improving the prognosis by newborn screening and early treatment. Pediatrics 124:e1116

    Article  PubMed  Google Scholar 

  4. Civallero G, Michelin K, Mari J, Viapiana M, Burin M, Coelho JC, Giugliani R (2006) Twelve different enzyme assays on dried-blood filter paper samples for detection of patients with selected inherited lysosomal storage diseases. Clin Chim Acta 372:98–102

    Article  PubMed  CAS  Google Scholar 

  5. Gasparotto N, Tomanin R, Frigo AC, Niizawa G, Pasquini E, Blanco M, Donati MA, Keutzer J, Zacchello F, Scarpa M (2009) Rapid diagnostic testing procedures for lysosomal storage disorders: α-glycosidase and β-galactosidase assays on dried blood spots. Clin Chim Acta 402:38–41

    Article  PubMed  CAS  Google Scholar 

  6. Horn PS, Pesce AJ (2003) Reference intervals: an update. Clin Chim Acta 334:5–23

    Article  PubMed  CAS  Google Scholar 

  7. Kemper AR, Hwu WL, Lloyd-Puryear M, Kishnani PS (2007) Newborn screening for Pompe disease: synthesis of the evidence and development of screening recommendations. Pediatrics 120:1327–1334

    Article  Google Scholar 

  8. Lukacs Z, Cobos PN, Mengel E, Hartung R, Beck M, Deschauer M, Keil A, Santer R (2010) Diagnostic efficacy of the fluorometric determination of enzyme activity for Pompe disease from dried blood specimens compared with lymphocytes—possibility for newborn screening. J Inherit Metab Dis 33:43–50

    Article  PubMed  CAS  Google Scholar 

  9. Lukacs Z, Hartung R, Beck M, Keil A, Mengel E (2007) Direct comparison of enzyme measurements from dried blood and leukocytes from male and female Fabry disease patients. J Inherit Metab Dis 30:614

    Article  PubMed  CAS  Google Scholar 

  10. Marsden D, Levy H (2010) Newborn screening of lysosomal storage disorders. Clin Chem 567:1071–1079

    Article  Google Scholar 

  11. Mechtler TP, Stary S, Metz TF, De Jesús VR, Greber-Platzer S, Pollak A, Herkner KR, Streubel B, Kasper DC (2012) Neonatal screening for lysosomal storage disorders: feasibility and incidence from a nationwide study in Austria. Lancet 379:335–341

    Article  PubMed  Google Scholar 

  12. Meikle MJ, Grasby DJ, Dean DJ, Lang DL, Bockmann M, Whittle AM, Fietz MJ, Simonsen H, Fuller M, Brooks DA, Hopwood JJ (2006) Newborn screening for lysosomal storage disorders. Mol Genet Metab 88:307–314

    Article  PubMed  CAS  Google Scholar 

  13. Müller KB, Rodrigues MDB, Pereira VG, Martins AM, D'Almeida V. (2010) Reference values for lysosomal enzymes activities using dried blood spots samples - a Brazilian experience. Diagn Pathol 5 65. doi:10.1186/1746-1596-5-65

  14. Nakamura K, Hattori K, Endo F (2011) Newborn screening for lysosomal storage disorders. Am J Med Genet C 157:63–71

    Article  CAS  Google Scholar 

  15. National Committee for Clinical Laboratory Standards (2001) How to define and determine reference intervals in the clinical laboratory: approved guideline, NCCLS document C28-A and C28-A2. Villanova, NCCLS

    Google Scholar 

  16. Pastores GM (2010) Lysosomal storage disorders. Principles and Practices. World Scientific, Singapore, pp 5–15

    Google Scholar 

  17. Reusera AJ, Verheijena FW, Balib D, van Diggelena OP, Germain DP, Hwud WL, Lukacse Z, Mühlf A, Olivovag P, Piraudh M, Wuytsi B, Zhang K, Keutzerg J (2011) The use of dried blood spot samples in the diagnosis of lysosomal storage disorders—current status and perspectives. Mol Genet Metab 104:144–148

    Article  Google Scholar 

  18. Shigeto S, Katafuchi T, Okada Y, Nakamura K, Endo F, Okuyama T, Takeuchi H, Kroos MA, Verheijen FW, Reuser AJJ, Okumiya T (2011) Improved assay for differential diagnosis between Pompe disease and acid α-glycosidase pseudodeficiency on dried blood spots. Mol Genet Metab 103:12–17

    Article  PubMed  CAS  Google Scholar 

  19. Sözmen EY (2012) Sample blank subtraction outreachs hemoglobin interferences in flurorometric methods for DBS. Mol Genet Metab 105:530

    Article  PubMed  Google Scholar 

  20. Spada M, Pagliardini S, Yasuda M, Tukel T, Thiagarajan T, Sakuraba H, Ponzone A, Desnick RJ (2006) High incidence of later-onset Fabry disease revealed by newborn screening. Am J Hum Genet 79:31–40

    Article  PubMed  CAS  Google Scholar 

  21. Staretz-Chacham O, Lang TC, LaMarca ME, Krasnewich D, Sidransky E (2009) Lysosomal storage disorders in the newborn. Pediatrics 123:1191

    Article  PubMed  Google Scholar 

  22. Zhang H, Kallwass H, Young SP, Carr C, Dai J, Kishnani PS, Millington DS, Keutzer J, Chen YT, Bali D (2006) Comparison of maltose and acarbose as inhibitors of maltase-glucoamylase activity in assaying acid α-glucosidase activity in dried blood spots for the diagnosis of infantile Pompe disease. Genet Med 8:302–306

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We are grateful to Genzyme Corp. for the financial support and to Sundus Ekinci for the technical support in performing the enzymatic studies.

Conflicts of interest

The authors declare that there is no conflict of interest with any financial organization.

Author information

Authors and Affiliations

  1. Department of Medical Biochemistry, Ege University Faculty of Medicine, Bornova, Izmir, Turkey

    Ozan Aldemir, Pelin Ergun & Eser Y. Sözmen

  2. Department of Neonatalogy, Ege University Faculty of Medicine, Izmir, Turkey

    Sezgin Güneş, Özge Altun Köroğlu, Mehmet Yalaz & Nilgün Kültürsay

  3. Department of Pediatric Metabolism, Ege University Faculty of Medicine, Izmir, Turkey

    Mahmut Çoker

Authors
  1. Ozan Aldemir
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pelin Ergun
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sezgin Güneş
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Özge Altun Köroğlu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mehmet Yalaz
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nilgün Kültürsay
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mahmut Çoker
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Eser Y. Sözmen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eser Y. Sözmen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Aldemir, O., Ergun, P., Güneş, S. et al. Reference intervals of α-glycosidase, β-glycosidase, and α-galactosidase in dried blood spot in a Turkish newborn population. Eur J Pediatr 172, 1221–1227 (2013). https://doi.org/10.1007/s00431-013-2026-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00431-013-2026-3

Keywords

Search

Navigation