Available online 16 April 2024

What is already known about this topic?

IEIs are inherited disorders characterized by an increased susceptibility to life threatening infectious diseases, autoimmunity, and malignant diseases with a high mortality rate in the first years of life.

What does this article add to our knowledge?

Twenty years after the introduction of NBS for primary immunodeficiency we report on an expanded NBS program for IEIs. The program increased our diagnostic rate and consequentially improved care for patients and their families.

How does this study impact current management guidelines?

All patients with an IEI benefit from early management. An expanded NBS strategy has the potential to enhance diagnostic accuracy for IEIs and potentially reduces delays in introducing treatment.

Inborn errors of immunity (IEIs) include 485 inherited disorders characterized by an increased susceptibility to life threatening infectious diseases, autoimmunity and malignant diseases with a high mortality rate in the first years of life. Severe Combined Immunodeficiency is the most severe of the IEIs and its detection should be a primary goal in a newborn screening (NBS) program. The term "actionable" has recently been used for all IEIs with outcomes that can be demonstrably improved through early specialized intervention.

Objective: to evaluate the results of the expanded NBS strategy for IEIs in Tuscany Region (Italy), based on TREC (T-cell Receptor Excision Circles), KREC (Kappa Recombining Excision Circles) and Tandem Mass-based assays.

This is a retrospective study collecting data from all infants born in Tuscany from October 10, 2018, to October 10, 2022. Tandem mass assay to identify Adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) deficiency, together with TREC and KREC molecular analysis were conducted on dried blood spot (DBS) from the newborns’ Guthrie Cards. A new DBS and evaluation by an immunologist were carried out when the results of the first test were outside the diagnostic cut-offs.

94,319 newborns were evaluated. Referral rates for TREC (0.031%) and KREC (0.074%) in this study are in line with the data available in literature. The results from the expanded NBS strategy revealed an incidence rate of 1/9,431 affected newborns.

This work represents the first description of a sustainable and real-life based expanded NBS program for IEIs with a high diagnostic incidence facilitating prompt management of identified patients.

© 2024 Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology