In 2008, newborn screening (NBS) for severe combined immunodeficiency (SCID) began as a pilot study in Wisconsin and has recently been added to every state’s newborn screen panel. The incidence of SCID is estimated at 1 per 58,000 births which may suggest infrequent NBS SCID screen positive results in states with low annual birth rates. In this study, we report our center’s experience with NBS positive SCID screen referrals over a 10-year period. A total of 68 full-term newborns were referred to our center for confirmatory testing. Of these referrals, 50% were false positives, 12% were SCID diagnoses, 20% syndromic T cell lymphopenia (TCL) disorders, and 18% non-SCID, non-syndromic TCL. Through collaboration with our newborn screening lab, second-tier targeted gene sequencing was performed for newborns with SCID screen positive results from communities with known founder pathogenic variants and provided rapid genetic confirmation of SCID and non-SCID TCL disorders. Despite extensive genetic testing, two of the eight (25%) identified newborns with SCID diagnoses lacked a definable genetic defect. Additionally, our referrals included ten newborns who were otherwise healthy newborns with idiopathic TCL and varied CD3+ T cell number longitudinal trajectories. Collectively, referrals to our single site over a 10-year period describe a broad spectrum of medically actionable and idiopathic TCL disorders which highlight the importance of clinical immunology expertise in all states, demonstrate efficiencies and challenges for second-tier genetic testing, and further emphasize the need to development standardized evaluation algorithms for non-SCID TCL.

2008 年，新生儿重症联合免疫缺陷 (SCID) 筛查 (NBS) 作为一项试点研究在威斯康星州开始，最近已被添加到每个州的新生儿筛查小组中。SCID 的发病率估计为每 58,000 例新生儿中有 1 例，这可能表明在年出生率较低的州中 NBS SCID 筛查阳性结果很少。在这项研究中，我们报告了我们中心过去 10 年在 NBS 阳性 SCID 筛查转诊方面的经验。共有 68 名足月新生儿被转诊到我们的中心进行确认性检测。在这些转诊中，50% 为假阳性，12% 为 SCID 诊断，20% 为综合征 T 细胞淋巴细胞减少症 (TCL) 疾病，18% 为非 SCID、非综合征 TCL。通过与我们的新生儿筛查实验室合作，对来自具有已知创始人致病变异的社区的 SCID 筛查阳性结果的新生儿进行了二级靶向基因测序，并为 SCID 和非 SCID TCL 疾病提供了快速的基因确认。尽管进行了广泛的基因检测，但在被诊断为 SCID 的 8 名新生儿中，有 2 名 (25%) 缺乏可定义的遗传缺陷。此外，我们的转诊包括 10 名患有特发性 TCL 和不同 CD3+ T 细胞数量纵向轨迹的健康新生儿。总的来说，在 10 年期间对我们单一站点的转诊描述了广泛的医学上可操作和特发性 TCL 疾病，这些疾病突出了临床免疫学专业知识在所有州的重要性，证明了二级基因检测的效率和挑战，