Skip to main content
Top
Published in: Journal of Clinical Immunology 5/2020

01-07-2020 | Immunodeficiency | Original Article

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

Authors: Sonu Shai, Ruy Perez-Becker, Oliver Andres, Shahrzad Bakhtiar, Ulrich Bauman, Horst von Bernuth, Carl-Friedrich Classen, Gregor Dückers, Sabine M. El-Helou, Andrea Gangfuß, Sujal Ghosh, Bodo Grimbacher, Fabian Hauck, Manfred Hoenig, Ralf A. Husain, Gerhard Kindle, Florian Kipfmueller, Christian Klemann, Renate Krüger, Elke Lainka, Kai Lehmberg, Florens Lohrmann, Henner Morbach, Nora Naumann-Bartsch, Prasad Thomas Oommen, Ansgar Schulz, Kathrin Seidemann, Carsten Speckmann, Karl-Walter Sykora, Rüdiger von Kries, Tim Niehues

Published in: Journal of Clinical Immunology | Issue 5/2020

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference Puck JM. Newborn screening for severe combined immunodeficiency and T-cell lymphopenia. Immunol Rev. 2019;287:241–52.CrossRef Puck JM. Newborn screening for severe combined immunodeficiency and T-cell lymphopenia. Immunol Rev. 2019;287:241–52.CrossRef
2.
go back to reference Fischer A, Notarangelo LD, Neven B, Cavazzana M, Puck JM. Severe combined immunodeficiencies and related disorders. Nat Rev Dis Prim. 2015;1:15061.CrossRef Fischer A, Notarangelo LD, Neven B, Cavazzana M, Puck JM. Severe combined immunodeficiencies and related disorders. Nat Rev Dis Prim. 2015;1:15061.CrossRef
3.
go back to reference Pai S-Y, Logan BR, Griffith LM, Buckley RH, Parrott RE, Dvorak CC, et al. Transplantation outcomes for severe combined immunodeficiency, 2000–2009. N Engl J Med. 2014;371:434–46.CrossRef Pai S-Y, Logan BR, Griffith LM, Buckley RH, Parrott RE, Dvorak CC, et al. Transplantation outcomes for severe combined immunodeficiency, 2000–2009. N Engl J Med. 2014;371:434–46.CrossRef
4.
go back to reference Heimall J, Logan BR, Cowan MJ, Notarangelo LD, Griffith LM, Puck JM, et al. Immune reconstitution and survival of 100 SCID patients post-hematopoietic cell transplant: a PIDTC natural history study. Blood. 2017;130:2718–27.CrossRef Heimall J, Logan BR, Cowan MJ, Notarangelo LD, Griffith LM, Puck JM, et al. Immune reconstitution and survival of 100 SCID patients post-hematopoietic cell transplant: a PIDTC natural history study. Blood. 2017;130:2718–27.CrossRef
5.
go back to reference Brown L, Xu-Bayford J, Allwood Z, Slatter M, Cant A, Davies EG, et al. Neonatal diagnosis of severe combined immunodeficiency leads to significantly improved survival outcome: the case for newborn screening. Blood. 2011;117:3243–6.CrossRef Brown L, Xu-Bayford J, Allwood Z, Slatter M, Cant A, Davies EG, et al. Neonatal diagnosis of severe combined immunodeficiency leads to significantly improved survival outcome: the case for newborn screening. Blood. 2011;117:3243–6.CrossRef
6.
go back to reference Cirillo E, Cancrini C, Azzari C, Martino S, Martire B, Pession A, et al. Clinical, immunological, and molecular features of typical and atypical severe combined immunodeficiency: report of the italian primary immunodeficiency network. Front Immunol. 2019;10. Cirillo E, Cancrini C, Azzari C, Martino S, Martire B, Pession A, et al. Clinical, immunological, and molecular features of typical and atypical severe combined immunodeficiency: report of the italian primary immunodeficiency network. Front Immunol. 2019;10.
7.
go back to reference Al-Harthi L, Marchetti G, Steffens CM, et al. Detection of T cell receptor circles (TRECs) as biomarkers for de novo T cell synthesis using a quantitative polymerase chain reaction-enzyme linked immunosorbent assay (PCR-ELISA). J Immunol Methods. 2000;237:187–97.CrossRef Al-Harthi L, Marchetti G, Steffens CM, et al. Detection of T cell receptor circles (TRECs) as biomarkers for de novo T cell synthesis using a quantitative polymerase chain reaction-enzyme linked immunosorbent assay (PCR-ELISA). J Immunol Methods. 2000;237:187–97.CrossRef
8.
go back to reference Weinberg K, Annett G, Kashyap A, Lenarsky C, Forman SJ, Parkman R. The effect of thymic function on immunocompetence following bone marrow transplantation. Biol Blood Marrow Transplant. 1995;1:18–23.PubMed Weinberg K, Annett G, Kashyap A, Lenarsky C, Forman SJ, Parkman R. The effect of thymic function on immunocompetence following bone marrow transplantation. Biol Blood Marrow Transplant. 1995;1:18–23.PubMed
9.
go back to reference Jamieson BD, Douek DC, Killian S, Hultin LE, Scripture-Adams DD, Giorgi JV, et al. Generation of functional thymocytes in the human adult. Immunity. 1999;10:569–75.CrossRef Jamieson BD, Douek DC, Killian S, Hultin LE, Scripture-Adams DD, Giorgi JV, et al. Generation of functional thymocytes in the human adult. Immunity. 1999;10:569–75.CrossRef
10.
go back to reference Schatorjé EJH, Gemen EFA, Driessen GJA, Leuvenink J, van Hout RWNM, de Vries E. Paediatric reference values for the peripheral T cell compartment. Scand J Immunol. 2012;75:436–44.CrossRef Schatorjé EJH, Gemen EFA, Driessen GJA, Leuvenink J, van Hout RWNM, de Vries E. Paediatric reference values for the peripheral T cell compartment. Scand J Immunol. 2012;75:436–44.CrossRef
13.
go back to reference Puck JM. Lessons for sequencing from the addition of severe combined immunodeficiency to newborn screening panels. Hast Cent Rep. 2018;48:S7–9.CrossRef Puck JM. Lessons for sequencing from the addition of severe combined immunodeficiency to newborn screening panels. Hast Cent Rep. 2018;48:S7–9.CrossRef
14.
go back to reference Nourizadeh M, Borte S, Fazlollahi MR, et al. A new IL-2RG gene mutation in an X-linked SCID identified through TREC/KREC screening: a case report. Iran J Allergy Asthma Immunol. 2015;14:457–61.PubMed Nourizadeh M, Borte S, Fazlollahi MR, et al. A new IL-2RG gene mutation in an X-linked SCID identified through TREC/KREC screening: a case report. Iran J Allergy Asthma Immunol. 2015;14:457–61.PubMed
15.
go back to reference Thomas C, Durand-Zaleski I, Frenkiel J, Mirallié S, Léger A, Cheillan D, et al. Clinical and economic aspects of newborn screening for severe combined immunodeficiency: DEPISTREC study results. Clin Immunol. 2019;202:33–9.CrossRef Thomas C, Durand-Zaleski I, Frenkiel J, Mirallié S, Léger A, Cheillan D, et al. Clinical and economic aspects of newborn screening for severe combined immunodeficiency: DEPISTREC study results. Clin Immunol. 2019;202:33–9.CrossRef
16.
go back to reference Routes JM, Grossman WJ, Verbsky J, et al. Statewide newborn screening for severe T-cell lymphopenia. JAMA. 2009;302:2465–70.CrossRef Routes JM, Grossman WJ, Verbsky J, et al. Statewide newborn screening for severe T-cell lymphopenia. JAMA. 2009;302:2465–70.CrossRef
17.
go back to reference Dorsey MJ, Puck JM. Newborn screening for severe combined immunodeficiency in the United States. Immunol Allergy Clin N Am. 2019;39:1–11.CrossRef Dorsey MJ, Puck JM. Newborn screening for severe combined immunodeficiency in the United States. Immunol Allergy Clin N Am. 2019;39:1–11.CrossRef
18.
go back to reference Chien Y-H, Chiang S-C, Chang K-L, Yu HH, Lee WI, Tsai LP, et al. Incidence of severe combined immunodeficiency through newborn screening in a Chinese population. J Formos Med Assoc. 2015;114:12–6.CrossRef Chien Y-H, Chiang S-C, Chang K-L, Yu HH, Lee WI, Tsai LP, et al. Incidence of severe combined immunodeficiency through newborn screening in a Chinese population. J Formos Med Assoc. 2015;114:12–6.CrossRef
19.
go back to reference Rechavi E, Lev A, Simon AJ, Stauber T, et al. First year of Israeli newborn screening for severe combined immunodeficiency—clinical achievements and insights. Front Immunol. 2017;8:1448 eCollection.CrossRef Rechavi E, Lev A, Simon AJ, Stauber T, et al. First year of Israeli newborn screening for severe combined immunodeficiency—clinical achievements and insights. Front Immunol. 2017;8:1448 eCollection.CrossRef
20.
go back to reference Somech R, Etzioni A. A call to include severe combined immunodeficiency in newborn screening program. Rambam Maimonides Med J. 2014;5:e0001.CrossRef Somech R, Etzioni A. A call to include severe combined immunodeficiency in newborn screening program. Rambam Maimonides Med J. 2014;5:e0001.CrossRef
21.
go back to reference Ebrahimi-Fakhari D, Zemlin M, Sauer H, et al. Erhebungseinheit für seltene pädiatrische Erkrankungen in Deutschland (ESPED) – 25 Jahre pädiatrische Epidemiologie: Eine Bestandsaufnahme. Klin Pädiatrie. 2018;230:215–24.CrossRef Ebrahimi-Fakhari D, Zemlin M, Sauer H, et al. Erhebungseinheit für seltene pädiatrische Erkrankungen in Deutschland (ESPED) – 25 Jahre pädiatrische Epidemiologie: Eine Bestandsaufnahme. Klin Pädiatrie. 2018;230:215–24.CrossRef
22.
go back to reference Göbel U, Heinrich B, Krauth K, Steingrüber HJ, Kries R. Evaluation der Prozess- und Ergebnisqualität der Erhebungseinheit für seltene pädiatrische Erkrankungen in Deutschland (ESPED). Klin Pädiatrie. 2010;222:92–7.CrossRef Göbel U, Heinrich B, Krauth K, Steingrüber HJ, Kries R. Evaluation der Prozess- und Ergebnisqualität der Erhebungseinheit für seltene pädiatrische Erkrankungen in Deutschland (ESPED). Klin Pädiatrie. 2010;222:92–7.CrossRef
23.
go back to reference Hook EB, Regal RR. Capture-recapture methods in epidemiology: methods and limitations. Epidemiol Rev. 1995;17:243–64.CrossRef Hook EB, Regal RR. Capture-recapture methods in epidemiology: methods and limitations. Epidemiol Rev. 1995;17:243–64.CrossRef
24.
go back to reference Chao A, Tsay PK, Lin SH, Shau WY, Chao DY. The applications of capture-recapture models to epidemiological data. Stat Med. 2001;20:3123–57.CrossRef Chao A, Tsay PK, Lin SH, Shau WY, Chao DY. The applications of capture-recapture models to epidemiological data. Stat Med. 2001;20:3123–57.CrossRef
25.
26.
go back to reference Woodbine L, Neal JA, Sasi N-K, Shimada M, Deem K, Coleman H, et al. PRKDC mutations in a SCID patient with profound neurological abnormalities. J Clin Invest. 2013;123:2969–80.CrossRef Woodbine L, Neal JA, Sasi N-K, Shimada M, Deem K, Coleman H, et al. PRKDC mutations in a SCID patient with profound neurological abnormalities. J Clin Invest. 2013;123:2969–80.CrossRef
27.
go back to reference De Pagter APJ, Bredius RGM, Kuijpers TW, et al. Overview of 15-year severe combined immunodeficiency in the Netherlands: towards newborn blood spot screening on behalf of the Dutch Working Party for Immunodeficiencies. Eur J Pediatr. 2015;174(9):1183–8.CrossRef De Pagter APJ, Bredius RGM, Kuijpers TW, et al. Overview of 15-year severe combined immunodeficiency in the Netherlands: towards newborn blood spot screening on behalf of the Dutch Working Party for Immunodeficiencies. Eur J Pediatr. 2015;174(9):1183–8.CrossRef
28.
go back to reference Amatuni GS, Currier RJ, Church JA, Bishop T, Grimbacher E, Nguyen AAC, et al. Newborn screening for severe combined immunodeficiency and T-cell lymphopenia in California, 2010–2017. Pediatrics. 2019;143:e20182300.CrossRef Amatuni GS, Currier RJ, Church JA, Bishop T, Grimbacher E, Nguyen AAC, et al. Newborn screening for severe combined immunodeficiency and T-cell lymphopenia in California, 2010–2017. Pediatrics. 2019;143:e20182300.CrossRef
29.
go back to reference Kwan A, Abraham RS, Currier R, Brower A, et al. Newborn screening for severe combined immunodeficiency in 11 screening programs in the United States. JAMA. 2014;312(7):729–38.CrossRef Kwan A, Abraham RS, Currier R, Brower A, et al. Newborn screening for severe combined immunodeficiency in 11 screening programs in the United States. JAMA. 2014;312(7):729–38.CrossRef
30.
go back to reference Picard C, Al-Herz W, Bousfiha A, et al. Primary immunodeficiency diseases: an update on the classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency 2015. J Clin Immunol. 2015;35:696–726.CrossRef Picard C, Al-Herz W, Bousfiha A, et al. Primary immunodeficiency diseases: an update on the classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency 2015. J Clin Immunol. 2015;35:696–726.CrossRef
31.
go back to reference Lacruz RS, Feske S. Diseases caused by mutations in ORAI1 and STIM1. Ann N Y Acad Sci. 2015;1356(1):45–79.CrossRef Lacruz RS, Feske S. Diseases caused by mutations in ORAI1 and STIM1. Ann N Y Acad Sci. 2015;1356(1):45–79.CrossRef
32.
go back to reference Heimall J, Cowan MJ. Long term outcomes of severe combined immunodeficiency: therapy implications. Expert Rev Clin Immunol. 2017;13(11):1029–40.CrossRef Heimall J, Cowan MJ. Long term outcomes of severe combined immunodeficiency: therapy implications. Expert Rev Clin Immunol. 2017;13(11):1029–40.CrossRef
34.
go back to reference Krantz MS, Stone CA, Connelly JA, et al. The effect of delayed and early diagnosis in siblings, and importance of newborn screening for SCID. Ann Allergy Asthma Immunol. 2019;122:211–3.CrossRef Krantz MS, Stone CA, Connelly JA, et al. The effect of delayed and early diagnosis in siblings, and importance of newborn screening for SCID. Ann Allergy Asthma Immunol. 2019;122:211–3.CrossRef
Metadata
Title
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
Authors
Sonu Shai
Ruy Perez-Becker
Oliver Andres
Shahrzad Bakhtiar
Ulrich Bauman
Horst von Bernuth
Carl-Friedrich Classen
Gregor Dückers
Sabine M. El-Helou
Andrea Gangfuß
Sujal Ghosh
Bodo Grimbacher
Fabian Hauck
Manfred Hoenig
Ralf A. Husain
Gerhard Kindle
Florian Kipfmueller
Christian Klemann
Renate Krüger
Elke Lainka
Kai Lehmberg
Florens Lohrmann
Henner Morbach
Nora Naumann-Bartsch
Prasad Thomas Oommen
Ansgar Schulz
Kathrin Seidemann
Carsten Speckmann
Karl-Walter Sykora
Rüdiger von Kries
Tim Niehues
Publication date
01-07-2020
Publisher
Springer US
Published in
Journal of Clinical Immunology / Issue 5/2020
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-020-00782-x

Other articles of this Issue 5/2020

Journal of Clinical Immunology 5/2020 Go to the issue