Newborn screening by tandem mass spectrometry confirms the high prevalence of sickle cell disease among German newborns
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.
KeywordsSickle cell disease Sickle cell anemia Newborn screening Tandem mass spectrometry Capillary electrophoresis
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 was obtained from all patients for being included in the study.
- 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
- 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
- 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
- 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.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
- 15.Statistisches Bundesamt (2018) Geburten 2016. https://www.destatis.de/DE/ZahlenFakten/GesellschaftStaat/Bevoelkerung/Geburten/Geburten.html
- 16.Nennstiel-Ratzel U (2018) DGNS Screeningreports. http://www.screening-dgns.de/reports.php
- 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
- 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
- 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.Bundesministerium der Justiz und für Verbraucherschutz (2016) Gesetz über genetische Untersuchungen bei Menschen. https://www.gesetze-im-internet.de/gendg/index.html