Sonu Shai1, Ruy Perez-Becker2, Oliver Andres3, Shahrzad Bakhtiar4, Ulrich Bauman5, Horst von Bernuth6,7,8, Carl-Friedrich Classen9, Gregor Dückers2, Sabine M El-Helou10,11,12,13, Andrea Gangfuß14, Sujal Ghosh15, Bodo Grimbacher10,11,16,17, Fabian Hauck18, Manfred Hoenig19, Ralf A Husain20, Gerhard Kindle10,21, Florian Kipfmueller22, Christian Klemann5, Renate Krüger6, Elke Lainka23, Kai Lehmberg24, Florens Lohrmann25, Henner Morbach3, Nora Naumann-Bartsch26, Prasad Thomas Oommen15, Ansgar Schulz19, Kathrin Seidemann27, Carsten Speckmann10,28, Karl-Walter Sykora29, Rüdiger von Kries30, Tim Niehues2. 1. Department of Paediatrics, Helios Klinikum Krefeld, Krefeld, Germany. sonu.shai@helios-gesundheit.de. 2. Department of Paediatrics, Helios Klinikum Krefeld, Krefeld, Germany. 3. Department of Paediatrics, University Hospital Würzburg, Würzburg, Germany. 4. Department for Children and Adolescents, Division for Stem Cell Transplantation and Immunology, Frankfurt University Hospital, Frankfurt a.M., Germany. 5. Department of Paediatric Pneumology, Allergy and Neonatology, Hannover Medical School, Hannover, Germany. 6. Department of Paediatric Pneumology, Immunology and Intensive Care, Charité- Universitätsmedizin, Berlin, Germany. 7. Department of Immunology, Labor Berlin GmbH, Berlin, Germany. 8. Berlin-Brandenburg Center for Regenerative Therapies, Berlin, Germany. 9. Department for Children and Adolescents, Oncology Hematology Division, University Medicine Rostock, Rostock, Germany. 10. Institute for Immunodeficiency, Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. 11. RESIST - Cluster of Excellence 2155 to Hanover Medical School, University of Freiburg, Freiburg, Germany. 12. Department of Clinical Immunology and Rheumatology, Hanover Medical School, Hanover, Germany. 13. Cluster of Excellence RESIST (EXC 2155), Hanover Medical School, Carl-Neuberg-Straße 1, 30625, Hanover, Germany. 14. Children's Hospital, University Duisburg-Essen, Essen, Germany. 15. Department of Paediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Centre for Child and Adolescent Health, University of Düsseldorf, Düsseldorf, Germany. 16. DZIF - German Center for Infection Research, Satellite Center Freiburg, Freiburg, Germany. 17. CIBSS - Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany. 18. Department of Paediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany. 19. Department of Paediatrics, University Medical Centre Ulm, Ulm, Germany. 20. University Children's Hospital, Jena, Germany. 21. FREEZE Biobank, Center for Biobanking, Medical Center, University of Freiburg, Freiburg, Germany. 22. Department of Neonatology and Paediatric Critical Care, University Children's Hospital Bonn, Bonn, Germany. 23. Children' s Hospital, University Duisburg-Essen, Paediatric Rheumatology, Essen, Germany. 24. Division of Paediatric Stem Cell Transplantation and Immunology, University Medical Center Hamburg Eppendorf, Hamburg, Germany. 25. University Medical Center Freiburg, Freiburg in Br., Germany. 26. Department of Paediatrics, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany. 27. Department of Paediatric Cardiology and Intensive Care Medicine, Medical School Hannover, Hannover, Germany. 28. Department of Paediatric and Adolescent Medicine, Division of Paediatric Hematology and Oncology, Faculty of Medicine, University of Freiburg, Freiburg, Germany. 29. Department of Paediatric Haematology and Oncology, Hannover Medical School, Hannover, Germany. 30. Institute of Social Paediatrics and Adolescent Medicine, University of Munich, Munich, Germany.
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.
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.
Authors: Anja Lüders; Oliver Blankenstein; Inken Brockow; Regina Ensenauer; Martin Lindner; Andreas Schulze; Uta Nennstiel Journal: Dtsch Arztebl Int Date: 2021-02-19 Impact factor: 5.594