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

Graafen L, Speckmann C, Bakhtiar S, Bernuth Hv, Lehmberg K, Bader P, Baumann U, Beier R, Borte S, Brockow I, Davies EG, Hartmann M, Holzer U, Klemann C, Kreins AY, Krüger R, Kontny U, Laws HJ, Meinhardt A, Morbach H, Naumann-Bartsch N, Rothoeft T, Schneider DT, Willasch A, Worth A, Seidel MG, Albert MH, Ehl S, Hauck F, Hönig M, Schulz A, Schuetz C, Ghosh S (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Book Volume: 46

Journal Issue: 1

DOI: 10.1007/s10875-026-01995-2

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.

Involved external institutions

Universitätsklinikum Düsseldorf Germany (DE) Universitätsklinikum Freiburg Germany (DE) Universitätsklinikum Frankfurt am Main (KGU) Germany (DE) Charité - Universitätsmedizin Berlin Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Klinikum St. Georg Germany (DE) Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit (LGL) Germany (DE) Great Ormond Street Hospital (GOSH) United Kingdom (GB) Universitätsklinikum Tübingen Germany (DE) Universitätsklinikum Leipzig Germany (DE) Universitätsklinikum Ulm Germany (DE) Universitätsklinikum Carl Gustav Carus Dresden Germany (DE) Universitätsklinikum Gießen und Marburg (UKGM) Germany (DE) Universitätsklinikum Würzburg Germany (DE) Katholisches Klinikum Bochum (St. Josef- und St. Elisabeth-Hospital gGmbH) Germany (DE) Klinikum Dortmund Germany (DE) Medizinische Universität Graz Austria (AT) Klinikum der Universität München (LMU Klinikum) Germany (DE) Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen Germany (DE)

How to cite

APA:

Graafen, L., Speckmann, C., Bakhtiar, S., Bernuth, H.v., Lehmberg, K., Bader, P.,... Ghosh, S. (2026). Syndromic Inborn Errors of Immunity in TREC-Newborn Screening: 5-year Experience from the German Screening Program. Journal of clinical immunology, 46(1). https://doi.org/10.1007/s10875-026-01995-2

MLA:

Graafen, Lea, et al. "Syndromic Inborn Errors of Immunity in TREC-Newborn Screening: 5-year Experience from the German Screening Program." Journal of clinical immunology 46.1 (2026).

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