Enhancing newborn health: expanded screening for immune disorders in Tuscany
Published: April 15, 2024
Inborn errors of immunity (IEIs) are genetic disorders that make children more prone to severe infections, autoimmune diseases and even cancers, often leading to high mortality rates in early childhood. Early diagnosis through newborn screening (NBS) programs is essential since it enables early treatment, which can significantly improve the prospects and quality of life of these children. Implementing extensive NBS strategies for IEIs and evaluating their outcomes is crucial.
In a recent study published in The Journal of Allergy and Clinical Immunology: In Practice, Ricci and Guarnieri et al. examined neonatal screening data of all newborns in Tuscany from October 2018 to October 2022. The screening involved the analysis of specific ‘DNA production waste' generated during T- and B-lymphocyte formation: T-cell receptor excision circles (TREC) and kappa-deleting recombination excision circles (KREC). TREC and KREC are markers that can be detected by real-time polymerase chain reaction (RT-PCR). Low or absent levels of TREC and/or KREC indicate immune defects of T and/or B cell line. In addition to potentially find more IEIs not identified by TREC and KREC, tandem mass spectrometry (TMS) was used to detect deficiencies in adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP), which are responsible for severe combined immunodeficiency (SCID) due to enzyme defects (ADA-SCID and PNP-SCID). Blood samples were collected by a small heel prick and analyzed on a Guthrie Card. In the event of abnormal results, the infants were called back -in the so called ‘referral procedure’- by the paediatric immunologist for early clinical evaluation, further blood tests to study the infant's immune system and genetic tests to confirm the presence of an IEIs.
The authors found that the expanded NBS strategy successfully identified 1 in 9,431 infants with genetically defined IEIs, indicating a remarkable incidence rate with referral rates consistent with existing data. Among the ten diagnoses described in the study, the authors pointed out that they identified, not only forms of SCID, but also other types of IEIs that presented with varying degrees of severity. Screening for all actionable IEIs is crucial, as early diagnosis can significantly improve prognosis and quality of life through preventive, supportive, targeted or curative therapies in these infants. These results highlight the strength of this expanded screening approach, which is not only feasible but also highly advantageous, enabling early diagnosis and timely clinical and therapeutic management of children with IEIs.
The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.
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