The primary focus of neonatal screening is the early detection of asymptomatic infants with a range of serious diseases for which effective treatment is available and for which early diagnosis and intervention will prevent serious consequences. Severe combined immunodeficiency (SCID) is a congenital disorder of immune function that requires prompt diagnosis and treatment to prevent life-threatening infections, improving survival and quality of life. The absence of functional T and/or B lymphocytes in congenital immune disorders serves as a diagnostic criterion used for newborn screening. Currently, an early diagnostic method exists based on the detection of T and B lymphocyte receptor gene recombination products (TREC/KREC).
Newborn screening for inborn errors of immunity, characterized by T and/or B cell lymphopenia, was carried out in a pilot program in the 2 regions of the Republic of Belarus, over a 2-year period (2023–2025), encompassing 27,796 newborns. The number of T cell receptor excision circles (TREC) and kappa-deleting recombination excision circles (KREC) was measured using multiplex real-time quantitative PCR (RQ-PCR) on DNA isolated from dried blood spots of neonatal screening cards. The number of copies of TREC/KREC was calculated per 1 million leukocytes using the formula: [1,000,000 × SQ TREC (KREC)/SQ ALB/2].
Fourteen children were recalled for re-examination due to low TREC and/or KREC levels. However, upon retesting, TREC and KREC values were within the normal range. During screening, one child was found to have a low TREC copy number—433 copies (2,200–45,000 copies)—with a normal KREC copy number. Upon examination, the child had DiGeorge syndrome. One child with a normal TREC copy number had absent B lymphocytes, which was also confirmed by lymphocyte immunophenotyping. Based on genetic testing, he was diagnosed with X-linked agammaglobulinemia with a mutation in the BTK gene.
This is the first large-scale screening study in the Republic of Belarus with simultaneous detection of TREC and KREC, allowing the identification of newborns with defects in both T and B cells.
