Syndromic Inborn Errors of Immunity in TREC-Newborn Screening: 5-year Experience from the German Screening Program

TREC-NBS identifies patients with inborn errors of immunity (IEI) and syndromic features, but uncertainty remains regarding their immunological management. To address this, syndromic patients detected by TREC-NBS in Germany between August 2019 and April 2024 were systematically analyzed, including phenotype, treatment, and outcomes. National registries were screened, and data were completed by the treating centres. A total of 77 syndromic patients were identified, with 22 different gene defects found in 72 individuals (93.5%). Primary thymic deficiency was present in 64% (49/77), most commonly due to 22q11.2 deletion syndrome (62%). Common clinical features included congenital heart disease (57%), facial/skeletal abnormalities (53%), and neurological symptoms (36%). Definitive treatments were provided promptly in eligible patients, including 6 thymus transplants and 6 hematopoietic stem cell transplants (HSCT). A watch-and-wait approach was applied to the remaining patients, with 34% (22/65) receiving prophylactic treatment. Recovery of CD3 + T-cell counts was limited to a minority. Overall survival was 89%, with a median follow-up of 32 months (range 0.5-60). To conclude, this is the first comprehensive study of syndromic IEI patients identified through TREC-NBS. The findings show that the German healthcare system enables both early prophylactic care and timely access to definitive therapies. Moving forward, interdisciplinary collaboration will be key to developing evidence-based management guidelines for this challenging patient group.

Authors

Institutions

Publication Details

Journal
Journal of Clinical Immunology
Published
2026-03-14
DOI
https://doi.org/10.1007/s10875-026-01995-2
Primary Topic
Immunodeficiency and Autoimmune Disorders
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Syndromic Inborn Errors of Immunity in TREC-Newborn Screening: 5-year Experience from the German Screening Program

Christian Klemann, Rita Beier, Horst von Bernuth, Ansgar Schulz et al.
Journal of Clinical Immunology
Immunodeficiency and Autoimmune Disorders
article

Syndromic Inborn Errors of Immunity in TREC-Newborn Screening: 5-year Experience from the German Screening Program

Christian Klemann, Rita Beier, Horst von Bernuth, Ansgar Schulz, Ursula Holzer, H. Morbach, Alexandra Y. Kreins, Kai Lehmberg, André Willasch, Udo Kontny, Inken Brockow, Tobias Rothoeft, Stephan Borte, Andrea Meinhardt, Renate Krüger, Catharina Schuetz, Manfred Hönig, Shahrzad Bakhtiar, C. Speckmann, Nora Naumann-Bartsch, Lea Graafen, Maximilian Hartmann, Fabian Hauck, Markus G. Seidel, Hans-Jürgen Laws, Ulrich Baumann, Austen Worth, Dominik T. Schneider, Michael H. Albert, Peter Bader, E. Graham Davies, Sujal Ghosh, Stephan Ehl
article en

Abstract

TREC-NBS identifies patients with inborn errors of immunity (IEI) and syndromic features, but uncertainty remains regarding their immunological management. To address this, syndromic patients detected by TREC-NBS in Germany between August 2019 and April 2024 were systematically analyzed, including phenotype, treatment, and outcomes. National registries were screened, and data were completed by the treating centres. A total of 77 syndromic patients were identified, with 22 different gene defects found in 72 individuals (93.5%). Primary thymic deficiency was present in 64% (49/77), most commonly due to 22q11.2 deletion syndrome (62%). Common clinical features included congenital heart disease (57%), facial/skeletal abnormalities (53%), and neurological symptoms (36%). Definitive treatments were provided promptly in eligible patients, including 6 thymus transplants and 6 hematopoietic stem cell transplants (HSCT). A watch-and-wait approach was applied to the remaining patients, with 34% (22/65) receiving prophylactic treatment. Recovery of CD3 + T-cell counts was limited to a minority. Overall survival was 89%, with a median follow-up of 32 months (range 0.5-60). To conclude, this is the first comprehensive study of syndromic IEI patients identified through TREC-NBS. The findings show that the German healthcare system enables both early prophylactic care and timely access to definitive therapies. Moving forward, interdisciplinary collaboration will be key to developing evidence-based management guidelines for this challenging patient group.

Journal of Clinical ImmunologyVol. 46(1)
Goethe University Frankfurt (DE), Universität Hamburg (DE), Medical University of Graz (AT), Universitätsklinikum Gießen und Marburg (DE), University Hospitals of the Ruhr-University of Bochum (DE), Great Ormond Street Hospital (GB), Klinikum St. Georg (DE), University Medical Center Freiburg (DE), Medizinische Hochschule Hannover (DE), Humboldt-Universität zu Berlin (DE), Universitätsklinikum Erlangen (DE), Düsseldorf University Hospital (DE), Health and Safety Authority (IE), University Medical Center Hamburg-Eppendorf (DE), Vivantes Klinikum (DE), University Children's Hospital Tübingen (DE), University Hospital Leipzig (DE), Universitätsklinikum Würzburg (DE), Klinikum Dortmund (DE), German Centre for Cardiovascular Research (DE), University Hospital Frankfurt (DE), Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE), University Hospital Ulm (DE), University Hospital Carl Gustav Carus (DE), Institute of Infection and Immunity (CA), Heinrich Heine University Düsseldorf (DE), University College London (GB), Charité - Universitätsmedizin Berlin (DE), University of Tübingen (DE), Ludwig-Maximilians-Universität München (DE), RWTH Aachen University (DE)
Partnerships for the goals
Openalex Percentile: Top 21%
Immunodeficiency and Autoimmune Disorders
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.