Newborn screening efforts focusing on the quantification of T cell receptor excision circles (TRECs), as a biomarker for abnormal thymic production of T cells, have allowed for the identification and definitive treatment of severe combined immunodeficiency (SCID) in asymptomatic neonates. With the adoption of TREC quantification in Guthrie cards across the USA and abroad, typical, and atypical SCID constitutes only ~ 10% of cases identified with abnormal TRECs associated with T cell lymphopenia. Several other non-SCID-related conditions may be identified by newborn screening in a term infant. Thus, it is important for physicians to recognize that other factors, such as prematurity, are often associated with low TRECs initially, but often improve with age. This paper focuses on a challenge that immunologists face: the diagnostic evaluation and management of cases in which abnormal TRECs are associated with variants of T cell lymphopenia in the absence of a genetically defined form of typical or atypical SCID. Various syndromes associated with T cell impairment, secondary forms of T cell lymphopenia, and idiopathic T cell lymphopenia are identified using this screening approach. Yet there is no consensus or guidelines to assist in the evaluation and management of these newborns, despite representing 90% of the patients identified, resulting in significant work for the clinical teams until a diagnosis is made. Using a case-based approach, we review pearls relevant to the evaluation of these newborns, as well as the management dilemmas for the families and team related to the resolution of genetic ambiguities.

新生儿筛查工作重点关注 T 细胞受体切除环 (TREC) 的量化，TREC 作为 T 细胞胸腺生成异常的生物标志物，有助于识别和明确治疗无症状新生儿的严重联合免疫缺陷 (SCID)。随着美国和国外 Guthrie 卡采用 TREC 定量，典型和非典型 SCID 只占与 T 细胞淋巴细胞减少相关的异常 TREC 病例的约 10%。一些其他非 SCID 相关的病症可以通过足月婴儿的新生儿筛查来识别。因此，医生必须认识到其他因素（例如早产）最初通常与低 TREC 相关，但通常会随着年龄的增长而改善。本文重点讨论免疫学家面临的挑战：在不存在典型或非典型 SCID 遗传定义形式的情况下，对异常 TREC 与 T 细胞淋巴细胞减少变异相关的病例进行诊断评估和管理。使用这种筛查方法可以识别与 T 细胞损伤、继发性 T 细胞淋巴细胞减少症和特发性 T 细胞淋巴细胞减少症相关的各种综合征。然而，尽管这些新生儿占已确诊患者的 90%，但尚无共识或指南来协助评估和管理，导致临床团队在做出诊断之前需要做大量工作。使用基于案例的方法，我们回顾了与这些新生儿评估相关的珍珠，以及与解决遗传模糊性相关的家庭和团队的管理困境。