Given the substantial morbidity of congenital cytomegalovirus (cCMV) infection on child health, there is considerable interest in the question of whether every newborn infant should be screened for this infection, toward the goal of identifying infants that may benefit from early intervention, anticipatory monitoring, and (in some cases) antiviral therapy [...]
Newborn screening for inborn errors of immunity and spinal muscular atrophy (SMA) enables early identification of infants at risk for severe disorders, facilitating timely treatment and improved outcomes. This study describes the first Greek experience with combined screening for SMA and severe T- and B-cell lymphopenias using SMN1 exon 7 analysis and T-cell receptor excision circles (TREC)/kappa-deleting recombination excision circles (KREC) measurements, using a single dried blood spot (DBS) sample. In 2026, 29,460 newborns were screened using a commercially available in vitro diagnostic kit. TREC and KREC were assessed semi-quantitatively, while SMA screening was based on qualitative detection of the SMN1 exon 7 target. Of these, 2168 (7.36%) required duplicate retesting, with 481 requiring a second DBS sample. Among the 481 newborns for whom a second DBS card was requested, 469 cards were received. Of these, 446 were classified as negative, 13 remained inconclusive, 4 were referred for genetic/immunological confirmatory evaluation, 2 remained under immunological follow-up, and 4 demonstrated recovery on repeat testing. Confirmatory evaluation identified four clinically significant cases: two with SMA, one with severe T-cell lymphopenia associated with 22q11.2 deletion syndrome, and one with CHARGE syndrome. Several low TREC/KREC results normalized on repeat testing. This experience demonstrates the feasibility of combined screening and highlights the importance of appropriate follow-up and confirmatory evaluation.
Severe combined immunodeficiency (SCID) is a pediatric emergency in which affected infants appear healthy at birth and are typically diagnosed only after life-threatening infection develops, by which point survival after hematopoietic stem cell transplantation declines substantially. Newborn screening using T-cell receptor excision circles (TRECs), often paired with kappa-deleting recombination excision circles (KRECs), enables presymptomatic detection of SCID and other clinically significant T- and B-cell lymphopenias and has been adopted across much of the United States and Western Europe; however, Baltic and Eastern European programs remain largely absent from the published literature. We report the first two years of Latvia’s nationwide TREC/KREC newborn screening program (1 April 2023–31 March 2025), covering 26,217 newborns (>99% of live births), and examine its interface with Latvia’s universal birth-dose BCG vaccination policy. Screening cutoffs were revised during the study period, reducing recall rates from an initial 4.6%/6.2% (TRECs/KRECs) to an overall 1.06%. Of 14 infants referred for specialist evaluation, none had classical SCID, while 3 (21%) were diagnosed with clinically significant non-SCID T-cell lymphopenia—2 with 22q11.2 deletion (DiGeorge) syndrome and 1 with 11q terminal deletion (Jacobsen) syndrome. TREC values rose progressively with gestational age, whereas KREC values showed the inverse pattern, being highest in the most preterm infants—a divergence with implications for gestational-age-specific cutoff design. These findings demonstrate that population-wide TREC/KREC screening is feasible in a small national program, with diagnostic value beyond SCID to clinically actionable non-SCID lymphopenias and provide the first published experience of nationwide SCID newborn screening from a Baltic country.
Establishing a National Newborn Screening Stakeholder Workgroup offers a timely opportunity to rebuild a coherent national process for evaluating conditions for the Recommended Uniform Screening Panel (RUSP) [...]
Pompe disease, Krabbe disease, and mucopolysaccharidosis type I were added to the newborn screen in Indiana in 2020. Clinical and laboratory teams collaborated to determine optimal strategies for first- and second-tier testing on newborn screen prior to referral to the metabolism clinic. Our metabolism clinic has worked with neurology, cardiology, and hematology/oncology departments to determine and execute best initial work-up, therapeutic, and ongoing surveillance approaches to manage patients diagnosed with one of these lysosomal disorders on newborn screen. In the first five years of this screening, 27 patients have been diagnosed with Pompe disease (three infantile-onset, 24 late-onset), 13 patients with Krabbe disease (one early infantile, 12 late-onset), and five patients with mucopolysaccharidosis type I (three severe phenotype, one with attenuated phenotype, one with possible attenuated disease). Our experience in caring for these individuals has helped to further refine second-tier testing and our clinical evaluation and management of these patients.
