Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, 1111 Highland Avenue, 4139 WIMR, Madison, WI, 53705-2275, USA.
Division of Allergy and Immunology, Mayo Clinic Children's Center, Rochester, MN, USA.
J Clin Immunol. 2021 Apr;41(3):595-602. doi: 10.1007/s10875-020-00956-7. Epub 2021 Jan 7.
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，新生儿筛查（NBS）开始在威斯康星州进行严重联合免疫缺陷（SCID）试点研究，最近已被添加到每个州的新生儿筛查面板中。SCID 的发病率估计为每 58000 例出生 1 例，这可能表明在出生率较低的州，NBS SCID 筛查阳性结果不常见。在这项研究中，我们报告了我们中心在过去 10 年中对 NBS 阳性 SCID 筛查转诊的经验。共有 68 名足月新生儿被转介到我们中心进行确认性检测。在这些转介中，50%是假阳性，12%是 SCID 诊断，20%是综合征性 T 细胞淋巴细胞减少症（TCL）疾病，18%是非 SCID、非综合征性 TCL。通过与我们的新生儿筛查实验室合作，对来自已知致病变异体的社区中 SCID 筛查阳性结果的新生儿进行了二级靶向基因测序，快速确认了 SCID 和非 SCID TCL 疾病的遗传特征。尽管进行了广泛的基因检测，但 8 名（25%）被诊断为 SCID 的新生儿中有两名缺乏可定义的遗传缺陷。此外，我们的转介包括 10 名其他方面健康的新生儿，他们患有特发性 TCL 和不同的 CD3+T 细胞数量纵向轨迹。总的来说，在过去 10 年中，我们单一中心的转介描述了一系列广泛的可治疗的和特发性 TCL 疾病，突显了所有州都需要临床免疫学专业知识的重要性，展示了二级基因检测的效率和挑战，并进一步强调需要为非 SCID TCL 制定标准化评估算法。
