Newborn screening for PIDs using both TREC and KREC identifies late occurrence of B cells

Tuscany is the first region in Italy to have implemented a neonatal screening for congenital immunodeficiencies using both tandem mass spectrometry for early and late-onset adenosine deaminase and purine-nucleoside phosphorylase deficiency (1) and multiplex Real-Time PCR for TREC and KREC quantification on Dried Blood Spots (DBS) (2). The screening program with TREC and KREC started on December 2013 and , basing on the last data update of March 2017 , it has screened a total of 18981 newborns in these first 3 year s. We have had no cases of low or diminished TRECs but 5 cases of low/absent KRECs. The first newborn with absent KRECs was promptly diagnosed with XLA, the second is the case reported below in this paper and the other ones were false positive with normal number of CD19+ cells at flow cytometric assessment. At present, specificity and cost-effectiveness are the main concerns regarding its utilization in NBS projects. The risk of high recall rates for PIDs assessment must be evaluated in consideration of parental anxiety and follow-up costs of mild undefined immunological conditions. On the other hand, though requiring long follow-ups, early identification of patients with late -onset immunodeficiency would be an undeniable advantage as it would prevent permanent damage due to recurrent infections in pre-diagnosis period. TREC use for newborn screening (NBS) of SCID is well known (3) while KRECs potentialities are still to be determined on perspective studies in large cohorts of patients. The following is a case of late presentation of KREC and B cells identified by the screening.