biostudies-literatureKubala SAIntramural NIH HHS109182https://www.ebi.ac.uk/biostudies/studies/S-EPMC9756444biostudies-literatureUnknown245Newborn screening (NBS) for severe combined immunodeficiency (SCID) can identify infants with non-SCID T cell lymphopenia (TCL). The purpose of this study was to characterize the natural history and genetic findings of infants with non-SCID TCL identified on NBS. We analyzed data from 80 infants with non-SCID TCL in the mid-Atlantic region between 2012 and 2019. 66 patients underwent genetic testing and 41 (51%) had identified genetic variant(s). The most common genetic variants were thymic defects (33%), defects with unknown mechanisms (12%) and bone marrow production defects (5%). The genetic cohort had significantly lower median initial CD3+, CD4+, CD8+ and CD4/CD45RA+ T cell counts compared to the non-genetic cohort. Thirty-six (45%) had either viral, bacterial, or fungal infection; onClinical immunology (Orlando, Fla.)Natural history of infants with non-SCID T cell lymphopenia identified on newborn screen.PMC9756444Z99 AI999999Keller MDLederman HHeimall JLawrence MGAnzabi MPalacios-Kibler TYounger MEMKubala SAFord MKDeFelice MLLiang HSandhu AHarmon GBundy VWard BfalseNatural history of infants with non-SCID T cell lymphopenia identified on newborn screen.Newborn screening (NBS) for severe combined immunodeficiency (SCID) can identify infants with non-SCID T cell lymphopenia (TCL). The purpose of this study was to characterize the natural history and genetic findings of infants with non-SCID TCL identified on NBS. We analyzed data from 80 infants with non-SCID TCL in the mid-Atlantic region between 2012 and 2019. 66 patients underwent genetic testing and 41 (51%) had identified genetic variant(s). The most common genetic variants were thymic defects (33%), defects with unknown mechanisms (12%) and bone marrow production defects (5%). The genetic cohort had significantly lower median initial CD3+, CD4+, CD8+ and CD4/CD45RA+ T cell counts compared to the non-genetic cohort. Thirty-six (45%) had either viral, bacterial, or fungal infection; on2022-01-01T00:00:00Z2022 Dec2025-04-22T13:12:07.196Z2025-04-06T00:35:29.041ZS-EPMC97564443636864310.1016/j.clim.2022.109182