Retrospective Analysis of TREC Based Newborn Screening Results and Clinical Phenotypes in Infants with the 22q11 Deletion Syndrome

Purpose Population-based newborn screening using T-cell receptor excision circles (TREC) identifies infants with severe T-lymphopenia, seen in severe combined immunodeficiencies (SCID), but also infants with the 22q11 deletion syndrome (22q11DS). Methods for analysis of kappa-deleting recombination excision circles (KREC) help identifying infants with B-lymphopenia. We aimed to evaluate the occurrence of abnormal TREC or KREC newborn screening results in 22q11DS patients and assessed the clinical relevance of abnormal screening reports. Methods Simultaneous TREC and KREC analysis was performed on stored original Guthrie cards. Patients with abnormal screening reports were compared to patients with normal reports, regarding lymphocyte counts and clinical severity, obtained by retrospective analysis of medical charts. Results Of 48 included patients, nine (19 %) had abnormal TREC copy numbers. All 22q11DS patients with abnormal TRECs had CD3+ T-lymphopenia at the time of diagnosis, but only one patient had the complete DiGeorge syndrome. Identified 22q11DS patients with abnormal TREC copy numbers showed significantly lower CD8+ T-lymphocytes at time-of-diagnosis and were significantly more prone to viral infections, compared to 22q11DS patients with normal TREC copy numbers. All 22q11DS patients showed KREC copies within the normal range. Conclusions In this retrospective study a high proportion of 22q11DS patients were identified by TREC-based newborn screening. Although only one of them had the complete DiGeorge syndrome with no T-lymphocytes, all of them had T-lymphopenia and most of them had recurrent viral infections, as well as other medical problems, warranting early recognition of the syndrome.