Abstract：
Newborn screening (NBS) for severe inborn errors of immunity (IEI), affecting T lymphocytes, and implementing measurements of T cell receptor excision circles (TREC) has been shown to be effective in early diagnosis and improved prognosis of patients with these genetic disorders. Few studies conducted on smaller groups of newborns report results of NBS that also include measurement of kappa-deleting recombination excision circles (KREC) for IEI affecting B lymphocytes. A pilot NBS study utilizing TREC/KREC detection was conducted on 202,908 infants born in 8 regions of Russia over a 14-month period. One hundred thirty-four newborns (0.66‰) were NBS positive after the first test and subsequent retest, 41% of whom were born preterm. After lymphocyte subsets were assessed via flow cytometry, samples of 18 infants (0.09‰) were sent for whole exome sequencing. Confirmed genetic defects were consistent with autosomal recessive agammaglobulinemia in 1/18, severe combined immunodeficiency - in 7/18, 22q11.2DS syndrome - in 4/18, combined immunodeficiency - in 1/18 and trisomy 21 syndrome - in 1/18. Two patients in whom no genetic defect was found met criteria of (severe) combined immunodeficiency with syndromic features. Three patients appeared to have transient lymphopenia. Our findings demonstrate the value of implementing combined TREC/KREC NBS screening and inform the development of policies and guidelines for its integration into routine newborn screening programs.
摘要：
新生儿筛查（NBS）的严重先天性免疫错误（IEI），影响T淋巴细胞，和实施T细胞受体切除环(TREC)的测量已被证明对患有这些遗传性疾病的患者的早期诊断和改善预后有效。对较小的新生儿组进行的研究很少报告NBS的结果，其中还包括测量影响B淋巴细胞的IEI的κ缺失重组切除环（KREC）。在14个月的时间内，对俄罗斯8个地区出生的202,908名婴儿进行了利用TREC/KREC检测的NBS试点研究。一百三十四例新生儿(0.66‰)经首次检测和后续复检后NBS阳性,其中41%是早产。通过流式细胞术评估淋巴细胞亚群后，将18例婴儿（0.09‰）的样本送去进行全外显子组测序。已证实的遗传缺陷与1/18的常染色体隐性遗传性无丙种球蛋白血症，7/18的严重联合免疫缺陷，4/18的22q11.2DS综合征，1/18的联合免疫缺陷和21三体综合征一致。1/18。两名未发现遗传缺陷的患者符合具有综合征特征的（严重）联合免疫缺陷的标准。三名患者似乎有一过性淋巴细胞减少症。我们的发现证明了实施TREC/KRECNBS联合筛查的价值，并为将其纳入常规新生儿筛查计划的政策和指南的制定提供了信息。
