{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:27:23Z","timestamp":1790872043652,"version":"4.1.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Severe combined immunodeficiency (SCID) can be detected at birth through T-cell receptor excision circles (TREC) analysis in dried blood spots. This study summarizes the results of the consolidated SCID newborn screening (NBS) program in Catalonia (Spain) during the first seven years of program implementation (2017\u20132023).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Newborns were screened for SCID using the EnLite Neonatal TREC assay (cut-off: 20 copies\/\u03bcL), with confirmatory immunological and genetic testing performed in screen-positive cases. Definitive SCID diagnosis was established according to PIDTC-2022 definitions, while final diagnostic classification followed the recommendations provided by Blom et\u00a0al.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 420,263 screened newborns, 105 screened positive (0.02%). SCID was diagnosed in eight infants and congenital athymia in one, corresponding to an overall incidence of 1:46,753 live births. Identified genetic defects included\n                      <jats:italic>RAG2<\/jats:italic>\n                      (n=3),\n                      <jats:italic>PNP<\/jats:italic>\n                      (n=1),\n                      <jats:italic>IL2RG<\/jats:italic>\n                      (n=2),\n                      <jats:italic>DCLRE1C<\/jats:italic>\n                      (n=1), and\n                      <jats:italic>FOXI3<\/jats:italic>\n                      (n=1) (one case remained genetically undefined). Six patients underwent early hematopoietic stem cell transplantation, achieving favorable outcomes in five patients, with one death due to post-transplant complications. In addition, gene therapy (\n                      <jats:italic>IL2RG<\/jats:italic>\n                      ,\n                      <jats:italic>DCLRE1C<\/jats:italic>\n                      ) and thymic transplantation (\n                      <jats:italic>FOXI3<\/jats:italic>\n                      ) resulted in successful outcomes in the three remaining patients. Overall and event-free survival reached 88%. Median age at diagnosis was 9 days and median age at initiation of definitive therapy was 3 months. In addition to SCID cases, 53 newborns were diagnosed with non-SCID T-cell lymphopenia (1:7,939), including syndromic, idiopathic, and reversible forms. During follow-up, patients with idiopathic T-cell lymphopenia did not develop significant infectious or autoimmune complications, except for one case of autoimmune neutropenia. Thirty-three cases were classified as false positives (0.008%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The Catalonian SCID newborn screening program demonstrated high clinical effectiveness, enabling early definitive treatment and excellent survival outcomes with a low false-positive burden. In addition, systematic follow-up of non-SCID T-cell lymphopenia identified through SCID screening appears warranted. These findings support the sustainability and clinical value of universal SCID screening programs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1803232","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T04:20:45Z","timestamp":1776313245000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["SCID newborn screening: seven-year performance and outcomes including T-cell lymphopenia in Catalonia (Spain)"],"prefix":"10.3389","volume":"17","author":[{"given":"Ana","family":"Argudo-Ram\u00edrez","sequence":"first","affiliation":[{"name":"Section of Inborn Errors of Metabolism-IBC, Department of Biochemistry and Molecular Genetics, Biomedical Diagnostic Center (CDB), Hospital Cl\u00ednic of Barcelona","place":["Barcelona, Catalonia, 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G.","family":"Riviere","sequence":"additional","affiliation":[{"name":"Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d\u2019Hebron","place":["Barcelona, Catalonia, Spain"]},{"name":"Infection and Immunity Research Group, Vall d\u2019Hebron Research Institute (VHIR)","place":["Barcelona, Catalonia, Spain"]},{"name":"Department of Pediatrics, Universitat Aut\u00f2noma de Barcelona","place":["Barcelona, Catalonia, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Manuel","family":"Gonz\u00e1lez de Aledo-Castillo","sequence":"additional","affiliation":[{"name":"Section of Inborn Errors of Metabolism-IBC, Department of Biochemistry and Molecular Genetics, Biomedical Diagnostic Center (CDB), Hospital Cl\u00ednic of Barcelona","place":["Barcelona, Catalonia, Spain"]},{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS)","place":["Barcelona, Catalonia, 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