Positive Newborn Screening for Severe Combined Immunodeficiency: What Should the Pediatrician Do?

Abstract

Severe combined immunodeficiency (SCID) is a group of diseases characterized by low T-cell count and impaired T-cell function, resulting in severe cellular and humoral immune defects. If not diagnosed and treated promptly, infants affected by this condition can develop severe infections which will result in death. Delayed treatment can markedly reduce the survival outcome of infants with SCID. T-cell receptor excision circle (TREC) levels are measured on newborn screening to promptly identify infants with SCID. It is important for primary care providers and pediatricians to understand the approach to managing infants with positive TREC-based newborn screening as they may be the first contact for infants with SCID. Primary care providers should be familiar with providing anticipatory guidance to the family in regard to protective isolation, measures to minimize the risk of infection, and the coordination of care with the SCID coordinating center team of specialists. In this article, we use case-based scenarios to review the principles of TREC-based newborn screening, the genetics and subtypes of SCID, and management for an infant with a positive TREC-based newborn screen.

Current Status of Newborn Bloodspot Screening Worldwide 2024: A Comprehensive Review of Recent Activities (2020–2023)

“…Implementation of SCID NBS has resulted in the development of “SCID Compass”, an educational resource, funded by the USA government, for parents needing accurate information to assist in decisions about treatment and care for identified newborns [ 68 ]. A 2023 USA report reviewed the need for education for physicians, using case-based scenarios to review the principles of TREC-based NBS, the genetics and subtypes of SCID, and clinical management of a newborn with a positive SCID NBS result [ 69 ]. Further responding to physicians’ needs for better disease definitions when diagnosing SCID from NBS, the USA–Canada Primary Immune Deficiency Treatment Consortium (PIDTC) implemented and published updated definitions in 2022/2023 [ 70 , 71 ].…”

“…At least four reports in 2022 addressed various issues pertinent to NBS: a report providing initial evidence of the value of screening for adenosine deaminase deficiency (ADA) using MS/MS [ 255 ]; a report showing the benign nature of transcobalamin receptor deficiency and the assertion that its detection should be considered an incidental finding with the caveat that long-term data are needed to ascertain the long-term outcomes of identified children [ 256 ]; a report on online NBS education for expectant parents showing that virtual baby fairs are cost effective, convenient, and equitable [ 257 ]; and an evaluation of national data currently maintained in a federally-supported database (NewSTEPs) that showed, “ … potential usefulness of NewSTEPs for research if investments in higher-quality data are made ” [ 258 ]. Physician education was the subject of a 2023 report that used case-based scenarios to review SCID NBS results, the principles of TREC-based NBS, the genetics and subtypes of SCID, and patient management for a positive TREC-based screening result [ 69 ].…”

“…potential usefulness of NewSTEPs for research if investments in higher-quality data are made" [258]. Physician education was the subject of a 2023 report that used case-based scenarios to review SCID NBS results, the principles of TREC-based NBS, the genetics and subtypes of SCID, and patient management for a positive TREC-based screening result [69].…”