Prospective Newborn Screening for SCID in Germany: A first analysis by the Pediatric Immunology Working Group (API)
Author:
Speckmann Carsten1ORCID, Nennstiel Uta, Hönig Manfred, Albert Michael H., Ghosh Sujal, Schütz Catharina, Brockow Inken, Hörster Friederike, Niehues Tim, Ehl Stephan, Wahn Volker, Borte Stephan, Lehmberg Kai, Baumann Ulrich, Beier Rita, Krüger Renate, Kuehl Joern-Sven, Klemann Christian, Kontny Udo, Holzer Ursula, Meinhardt Andrea, Morbach Henner, Naumann Nora, Rothoeft Tobias, Kreins Alexandra Y, Davies Edward G, Schneider Dominik, von Bernuth Horst, Klingebiel Thomas, Hoffmann Georg, Schulz Ansgar, Hauck Fabian H
Affiliation:
1. University of Freiburg
Abstract
Abstract
Background
T-cell receptor excision circle (TREC)-based newborn screening (NBS) for severe combined immunodeficiencies (SCID) was introduced in Germany in August 2019.
Methods
Children with abnormal TREC-NBS were referred to a newly established network of Combined Immunodeficiency (CID) Clinics and Centers. The Working Group for Pediatric Immunology (API) and German Society for Newborn Screening (DGNS) performed 6-monthly surveys to assess the TREC-NBS process after 2.5 years.
Results
Among 1.9 million screened newborns, 88 patients with congenital T-cell lymphocytopenia were identified (25 SCID, 17 leaky SCID/Omenn Syndrome (OS)/idiopathic T-cell lymphocytopenia and 46 syndromic disorders). A genetic diagnosis was established in 88%. Twenty-six patients underwent hematopoietic stem cell transplantation (HSCT), 23/26 within 4 months of life. Of these, 25/26 (96%) were alive at last follow-up. Two patients presented with in-utero onset OS and died shortly after birth. Five patients with syndromic disorders underwent thymus transplantation. Eight syndromic patients deceased, all from non-immunological complications. TREC-NBS missed one patient, who later presented clinically, and one tracking failure occurred after an inconclusive screening result.
Conclusion
TREC-NBS was successfully incorporated into German NBS and represents the largest prospective European TREC-NBS cohort at this point. The incidence of SCID/leaky SCID/OS in Germany is approximately 1:54.000. The overall incidence of severe congenital T-cell lymphocytopenia is 1:21.000. The newly founded API-CID network facilitates tracking and treatment of identified patients. Short-term HSCT outcome was excellent, but NBS and transplant registries will remain essential to evaluate the long-term outcome and to compare results across the rising numbers of TREC-NBS programs across Europe.
Publisher
Research Square Platform LLC
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