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Incidence of SCID in Germany from 2014 to 2015 an ESPED* Survey on Behalf of the API*** Erhebungseinheit für Seltene Pädiatrische Erkrankungen in Deutschland (German Paediatric Surveillance Unit) ** Arbeitsgemeinschaft Pädiatrische Immunologie

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Abstract

Purpose

Severe combined immunodeficiencies (SCID) are a heterogeneous group of fatal genetic disorders, in which the immune response is severely impaired. SCID can be cured if diagnosed early. We aim to determine the incidence of clinically defined SCID cases, acquire data of reported cases and evaluate their possible prediction by newborn screening, before introduction of a general screening program in Germany.

Methods

The German Surveillance Unit for rare Paediatric Diseases (ESPED) prospectively queried the number of incident SCID cases in all German paediatric hospitals in 2014 and 2015. Inclusion criteria were (1) opportunistic or severe infections or clinical features associated with SCID (failure to thrive, lacking thymus or lymphatic tissue, dysregulation of the immune system, graft versus host reaction caused by maternal T cells), (2) dysfunctional T cell immunity or proof of maternal T cells and (3) exclusion of a secondary immunodeficiency such as human immunodeficiency virus (HIV) infection. In a capture-recapture analysis, cases were matched with cases reported to the European Society for Immunodeficiencies (ESID).

Results

Fifty-eight patients were initially reported to ESPED, 24 reports could be confirmed as SCID, 21 patients were less than 1 year old at time of diagnosis. One SCID case was reported to ESID only. The estimated incidence of SCID in Germany is 1.6/100,000 (1:62,500) per year in children less than 1 year of age. Most patients reported were symptomatic and mortality in regard to reported outcome was high (29% (6/22)). The majority of incident SCID cases were considered to be probably detectable by newborn screening.

Conclusions

SCID is a rare disease with significant mortality. Newborn screening may give the opportunity to improve the prognosis in a significant number of children with SCID.

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Acknowledgements

This project was initiated by the working group Arbeitsgemeinschaft Pädiatrische Immunologie (API). We thank Catharina Schütz (Dresden, Germany), Michael Albert (Munich, Germany) and Stephan Borte (Leipzig) for reviewing the manuscript.

We would like to thank DGKJ for supplying the ESPED fee (3000 Euro) and travel costs, Kirsten Mischke, Julia Schmelze from the Pediatric Registry for Stem Cell Transplantation (PRST) Hannover and Henrike Ritterbusch from the Centre for Chronic Immunodeficiency Freiburg, Sandra Steinmann as well as ESPED, Andrea Groth and Stefan Jurkschat for supporting this project. Patients for this study were in part revealed through the ESID Registry.

Funding

Documentation to this registry was supported by the Federal Ministry of Education and Research (BMBF grants 01GM0896, 01GM1111B, 01GM1517C, and 01EO1303).

Author information

Authors and Affiliations

  1. Department of Paediatrics, Helios Klinikum Krefeld, Krefeld, Germany

    Sonu Shai, Ruy Perez-Becker, Gregor Dückers & Tim Niehues

  2. Department of Paediatrics, University Hospital Würzburg, Würzburg, Germany

    Oliver Andres & Henner Morbach

  3. Department for Children and Adolescents, Division for Stem Cell Transplantation and Immunology, Frankfurt University Hospital, Frankfurt a.M., Germany

    Shahrzad Bakhtiar

  4. Department of Paediatric Pneumology, Allergy and Neonatology, Hannover Medical School, Hannover, Germany

    Ulrich Bauman & Christian Klemann

  5. Department of Paediatric Pneumology, Immunology and Intensive Care, Charité- Universitätsmedizin, Berlin, Germany

    Horst von Bernuth & Renate Krüger

  6. Department of Immunology, Labor Berlin GmbH, Berlin, Germany

    Horst von Bernuth

  7. Berlin-Brandenburg Center for Regenerative Therapies, Berlin, Germany

    Horst von Bernuth

  8. Department for Children and Adolescents, Oncology Hematology Division, University Medicine Rostock, Rostock, Germany

    Carl-Friedrich Classen

  9. Institute for Immunodeficiency, Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

    Sabine M. El-Helou, Bodo Grimbacher, Gerhard Kindle & Carsten Speckmann

  10. RESIST – Cluster of Excellence 2155 to Hanover Medical School, University of Freiburg, Freiburg, Germany

    Sabine M. El-Helou & Bodo Grimbacher

  11. Department of Clinical Immunology and Rheumatology, Hanover Medical School, Hanover, Germany

    Sabine M. El-Helou

  12. Cluster of Excellence RESIST (EXC 2155), Hanover Medical School, Carl-Neuberg-Straße 1, 30625, Hanover, Germany

    Sabine M. El-Helou

  13. Children’s Hospital, University Duisburg-Essen, Essen, Germany

    Andrea Gangfuß

  14. Department of Paediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Centre for Child and Adolescent Health, University of Düsseldorf, Düsseldorf, Germany

    Sujal Ghosh & Prasad Thomas Oommen

  15. DZIF – German Center for Infection Research, Satellite Center Freiburg, Freiburg, Germany

    Bodo Grimbacher

  16. CIBSS – Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany

    Bodo Grimbacher

  17. Department of Paediatrics, Dr. von Hauner Children’s Hospital, University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany

    Fabian Hauck

  18. Department of Paediatrics, University Medical Centre Ulm, Ulm, Germany

    Manfred Hoenig & Ansgar Schulz

  19. University Children’s Hospital, Jena, Germany

    Ralf A. Husain

  20. FREEZE Biobank, Center for Biobanking, Medical Center, University of Freiburg, Freiburg, Germany

    Gerhard Kindle

  21. Department of Neonatology and Paediatric Critical Care, University Children’s Hospital Bonn, Bonn, Germany

    Florian Kipfmueller

  22. Children’ s Hospital, University Duisburg-Essen, Paediatric Rheumatology, Essen, Germany

    Elke Lainka

  23. Division of Paediatric Stem Cell Transplantation and Immunology, University Medical Center Hamburg Eppendorf, Hamburg, Germany

    Kai Lehmberg

  24. University Medical Center Freiburg, Freiburg in Br., Germany

    Florens Lohrmann

  25. Department of Paediatrics, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany

    Nora Naumann-Bartsch

  26. Department of Paediatric Cardiology and Intensive Care Medicine, Medical School Hannover, Hannover, Germany

    Kathrin Seidemann

  27. Department of Paediatric and Adolescent Medicine, Division of Paediatric Hematology and Oncology, Faculty of Medicine, University of Freiburg, Freiburg, Germany

    Carsten Speckmann

  28. Department of Paediatric Haematology and Oncology, Hannover Medical School, Hannover, Germany

    Karl-Walter Sykora

  29. Institute of Social Paediatrics and Adolescent Medicine, University of Munich, Munich, Germany

    Rüdiger von Kries

Authors
  1. Sonu Shai
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  9. Sabine M. El-Helou
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  31. Tim Niehues
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Corresponding author

Correspondence to Sonu Shai.

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Ethics Statement

This study was approved by the ethics committee of the University of Essen in Essen, Germany (reference number 13-5651-BO). An informed consent by patients or their parents was not required by the ethics committees, since the acquired data were completely anonymous.

Conflict of Interest

Gerhard Kindle was partially funded by grants from the BMBF and ESID for the purpose of this research.

Sabine El-Helou was funded for her work in the German PID-NET registry by the Federal Ministry of Education and Research (BMBF: grant codes: 01GM0896, 01GM1111B and 01GM1517C), by the European Society for Immunodeficiencies (ESID), by the Care-for-Rare Foundation, by PROimmun e.V., and by a restricted grant from LFB.

The PRST is supported by the Deutsche Kinderkrebsstifung Grant No. DKS 2016.5 to K.-W. Sykora.

Tim Niehues receives travel reimbursements of the European Medicines Agency (EMA), the Pediatric Rheumatology JIR cohort (Lausanne, Switzerland), the Jeffrey Modell Foundation for Primary immunodeficiencies (New York, USA) and the PENTA group (Pediatric European Network Trial in AIDS) and author honoraria from uptodate.com (Waltham, Massachusetts, USA).

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Shai, S., Perez-Becker, R., Andres, O. et al. Incidence of SCID in Germany from 2014 to 2015 an ESPED* Survey on Behalf of the API*** Erhebungseinheit für Seltene Pädiatrische Erkrankungen in Deutschland (German Paediatric Surveillance Unit) ** Arbeitsgemeinschaft Pädiatrische Immunologie. J Clin Immunol 40, 708–717 (2020). https://doi.org/10.1007/s10875-020-00782-x

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