Advertisement

Newborn screening by tandem mass spectrometry confirms the high prevalence of sickle cell disease among German newborns

  • Stephan Lobitz
  • Jeannette Klein
  • Annemarie Brose
  • Oliver Blankenstein
  • Claudia Frömmel
Original Article

Abstract

Sickle cell disease (SCD) is a severe inherited blood disorder associated with significant morbidity and mortality in early childhood. Since simple interventions are available to prevent early fatal courses, SCD is a target condition of several national newborn screening (NBS) programs worldwide, but not in Germany. Traditionally, the diagnosis of SCD is made by high-performance liquid chromatography (HPLC), isoelectric focusing (IEF), or capillary electrophoresis (CE), but globally, most NBS programs in place are based on tandem mass spectrometry (MS/MS). Recently, several publications have shown that MS/MS is an appropriate screening technique to detect hemoglobin patterns suggestive of SCD in newborns, too. We have studied dried blood spot samples of 29,079 German newborns by both CE and MS/MS and observed a 100% congruence of test results. Seven babies had hemoglobin patterns characteristic of SCD (1:4154). Our study confirms that (a) the suitability of MS/MS as an adequate substitute for CE in NBS for SCD and (b) the high prevalence of SCD among German newborns. Our results support the thesis that German newborns should be screened for SCD by MS/MS.

Keywords

Sickle cell disease Sickle cell anemia Newborn screening Tandem mass spectrometry Capillary electrophoresis 

Notes

Acknowledgements

We are deeply indebted to Novartis Germany and KINDerLEBEN e.V. for funding the present study. We thank Yvonne Daniel, Charles Turner, and Neil Dalton (London) for their invaluable intellectual and practical support during the whole study. We would also like to thank all children and parents who supported this project by providing dried blood spot samples.

Compliance with ethical standards

Conflict of interest

Novartis has contributed the major funding of the present study. S.L. has received honoraria from Novartis, Nordic Pharma, Celgene, and Bluebird for the scientific presentations and for his participance in Advisory Boards. The other authors declare no conflicts of interest.

Informed consent

Informed consent was obtained from all patients for being included in the study.

References

  1. 1.
    Ware RE, de Montalembert M, Tshilolo L, Abboud MR (2017) Sickle cell disease. Lancet 390(10091):311–323.  https://doi.org/10.1016/S0140-6736(17)30193-9 CrossRefPubMedGoogle Scholar
  2. 2.
    Rees DC, Williams TN, Gladwin MT (2010) Sickle-cell disease. Lancet 376(9757):2018–2031.  https://doi.org/10.1016/S0140-6736(10)61029-X CrossRefPubMedGoogle Scholar
  3. 3.
    Piel FB, Steinberg MH, Rees DC (2017) Sickle cell disease. N Engl J Med 376(16):1561–1573.  https://doi.org/10.1056/NEJMra1510865 CrossRefPubMedGoogle Scholar
  4. 4.
    Ryan K, Bain BJ, Worthington D, James J, Plews D, Mason A, Roper D, Rees DC, de la Salle B, Streetly A, British Committee for Standards in H (2010) Significant haemoglobinopathies: guidelines for screening and diagnosis. Br J Haematol 149(1):35–49.  https://doi.org/10.1111/j.1365-2141.2009.08054.x CrossRefPubMedGoogle Scholar
  5. 5.
    Eastman JW, Wong R, Liao CL, Morales DR (1996) Automated HPLC screening of newborns for sickle cell anemia and other hemoglobinopathies. Clin Chem 42(5):704–710PubMedGoogle Scholar
  6. 6.
    Keren DF, Hedstrom D, Gulbranson R, Ou CN, Bak R (2008) Comparison of Sebia Capillarys capillary electrophoresis with the primus high-pressure liquid chromatography in the evaluation of hemoglobinopathies. Am J Clin Pathol 130(5):824–831.  https://doi.org/10.1309/AJCPQY80HZWHHGZF CrossRefPubMedGoogle Scholar
  7. 7.
    Serjeant GR, Serjeant BE (1993) Management of sickle cell disease; lessons from the Jamaican cohort study. Blood Rev 7(3):137–145CrossRefPubMedGoogle Scholar
  8. 8.
    Gaston MH, Verter JI, Woods G, Pegelow C, Kelleher J, Presbury G, Zarkowsky H, Vichinsky E, Iyer R, Lobel JS, Diamond S, Holbrook CT, Gill FM, Ritchey K, Falletta JM, For the Prophylactic Penicillin Study Group (1986) Prophylaxis with oral penicillin in children with sickle cell anemia. A randomized trial. N Engl J Med 314(25):1593–1599.  https://doi.org/10.1056/NEJM198606193142501 CrossRefPubMedGoogle Scholar
  9. 9.
    Panepinto JA, Magid D, Rewers MJ, Lane PA (2000) Universal versus targeted screening of infants for sickle cell disease: a cost-effectiveness analysis. J Pediatr 136(2):201–208CrossRefPubMedGoogle Scholar
  10. 10.
    Le PQ, Ferster A, Dedeken L, Vermylen C, Vanderfaeillie A, Rozen L, Heijmans C, Huybrechts S, Devalck C, Cotton F, Ketelslegers O, Dresse MF, Fils JF, Gulbis B (2017) Neonatal screening improves sickle cell disease clinical outcome in Belgium. J Med Screen.  https://doi.org/10.1177/0969141317701166
  11. 11.
    Streetly A, Sisodia R, Dick M, Latinovic R, Hounsell K, Dormandy E (2017) Evaluation of newborn sickle cell screening programme in England: 2010-2016. Arch Dis Child.  https://doi.org/10.1136/archdischild-2017-313213
  12. 12.
    Therrell BL Jr, Lloyd-Puryear MA, Eckman JR, Mann MY (2015) Newborn screening for sickle cell diseases in the United States: a review of data spanning 2 decades. Semin Perinatol 39(3):238–251.  https://doi.org/10.1053/j.semperi.2015.03.008 CrossRefPubMedGoogle Scholar
  13. 13.
    Vichinsky E, Hurst D, Earles A, Kleman K, Lubin B (1988) Newborn screening for sickle cell disease: effect on mortality. Pediatrics 81(6):749–755PubMedGoogle Scholar
  14. 14.
    Gulbis B, Ferster A, Cotton F, Lebouchard MP, Cochaux P, Vertongen F (2006) Neonatal haemoglobinopathy screening: review of a 10-year programme in Brussels. J Med Screen 13(2):76–78.  https://doi.org/10.1258/096914106777589650 CrossRefPubMedGoogle Scholar
  15. 15.
  16. 16.
    Nennstiel-Ratzel U (2018) DGNS Screeningreports. http://www.screening-dgns.de/reports.php
  17. 17.
    Lobitz S, Frommel C, Brose A, Klein J, Blankenstein O (2014) Incidence of sickle cell disease in an unselected cohort of neonates born in berlin, Germany. Eur J Hum Genet 22(8):1051–1053.  https://doi.org/10.1038/ejhg.2013.286 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Frommel C, Brose A, Klein J, Blankenstein O, Lobitz S (2014) Newborn screening for sickle cell disease: technical and legal aspects of a German pilot study with 38,220 participants. Biomed Res Int 2014:695828–695810.  https://doi.org/10.1155/2014/695828 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Kunz JB, Awad S, Happich M, Muckenthaler L, Lindner M, Gramer G, Okun JG, Hoffmann GF, Bruckner T, Muckenthaler MU, Kulozik AE (2016) Significant prevalence of sickle cell disease in Southwest Germany: results from a birth cohort study indicate the necessity for general newborn screening. Ann Hematol 95(3):397-402.  https://doi.org/10.1007/s00277-015-2573-y
  20. 20.
    Grosse R, Lukacs Z, Cobos PN, Oyen F, Ehmen C, Muntau B, Timmann C, Noack B (2015) The prevalence of sickle cell disease and its implication for newborn screening in Germany (Hamburg metropolitan area). Pediatr Blood Cancer 63:168–170.  https://doi.org/10.1002/pbc.25706 CrossRefPubMedGoogle Scholar
  21. 21.
    Moat SJ, Rees D, King L, Ifederu A, Harvey K, Hall K, Lloyd G, Morrell C, Hillier S (2014) Newborn blood spot screening for sickle cell disease by using tandem mass spectrometry: implementation of a protocol to identify only the disease states of sickle cell disease. Clin Chem 60(2):373–380.  https://doi.org/10.1373/clinchem.2013.210948 CrossRefPubMedGoogle Scholar
  22. 22.
    Boemer F, Ketelslegers O, Minon JM, Bours V, Schoos R (2008) Newborn screening for sickle cell disease using tandem mass spectrometry. Clin Chem 54(12):2036–2041.  https://doi.org/10.1373/clinchem.2008.106369 CrossRefPubMedGoogle Scholar
  23. 23.
    Daniel YA, Henthorn J (2016) Newborn screening for sickling and other haemoglobin disorders using tandem mass spectrometry: a pilot study of methodology in laboratories in England. J Med Screen 23(4):175–178.  https://doi.org/10.1177/0969141316631008 CrossRefPubMedGoogle Scholar
  24. 24.
    Renom G, Mereau C, Maboudou P, Perini JM (2009) Potential of the Sebia Capillarys neonat fast automated system for neonatal screening of sickle cell disease. Clin Chem Lab Med 47(11):1423–1432.  https://doi.org/10.1515/CCLM.2009.315 CrossRefPubMedGoogle Scholar
  25. 25.
    Moat SJ, Rees D, George RS, King L, Dodd A, Ifederu A, Ramgoolam T, Hillier S (2017) Newborn screening for sickle cell disorders using tandem mass spectrometry: three years’ experience of using a protocol to detect only the disease states. Ann Clin Biochem 54(5):601–611.  https://doi.org/10.1177/0004563217713788 PubMedCrossRefGoogle Scholar
  26. 26.
    Bundesministerium der Justiz und für Verbraucherschutz (2016) Gesetz über genetische Untersuchungen bei Menschen. https://www.gesetze-im-internet.de/gendg/index.html

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Pediatric Oncology and HematologyAmsterdam Street Children’s HospitalKölnGermany
  2. 2.Charité – Universitätsmedizin Berlin, Newborn Screening LaboratoryBerlinGermany
  3. 3.Labor Berlin Charité – Vivantes GmbHBerlinGermany

Personalised recommendations