Abstract
Severe combined immunodeficiency (SCID) includes a group of monogenic disorders presenting with severe T cell lymphopenia (TCL) and high mortality, if untreated. The newborn screen (NBS) for SCID, included in the recommended universal screening panel (RUSP), has been widely adopted across the US and in many other countries. However, there is a lack of consensus regarding follow-up testing to confirm an abnormal result. The Clinical Immunology Society (CIS) membership was surveyed for confirmatory testing practices for an abnormal NBS SCID result, which included consideration of gestational age and birth weight, as well as flow cytometry panels. Considerable variability was observed in follow-up practices for an abnormal NBS SCID with 49% confirming by flow cytometry, 39% repeating TREC analysis, and the remainder either taking prematurity into consideration for subsequent testing or proceeding directly to genetic analysis. More than 50% of respondents did not take prematurity into consideration when determining follow-up. Confirmation of abnormal NBS SCID in premature infants continues to be challenging and is handled variably across centers, with some choosing to repeat NBS SCID testing until normal or until the infant reaches an adjusted gestational age of 37 weeks. A substantial proportion of respondents included naïve and memory T cell analysis with T, B, and NK lymphocyte subset quantitation in the initial confirmatory panel. These results have the potential to influence the diagnosis and management of an infant with TCL as illustrated by the clinical cases presented herein. Our data indicate that there is clearly a strong need for harmonization of follow-up testing for an abnormal NBS SCID result.
Highlights
Severe combined immunodeficiency (SCID) includes a group of monogenic disorders, which are characterized by significant T cell lymphopenia (TCL) in the neonate, present either in isolation or with diminished counts in other lymphocyte subsets, including B and Natural Killer (NK) cells
It is widely implemented across the United States as a screening tool for SCID and related disorders with significant TCL [24]
Despite successful implementation of the newborn screen (NBS) SCID across the United States, there is currently little uniformity in screening and confirmatory testing strategies used by various state laboratories, tertiary centers, and consulting immunologists/providers
Summary
Severe combined immunodeficiency (SCID) includes a group of monogenic disorders, which are characterized by significant T cell lymphopenia (TCL) in the neonate, present either in isolation or with diminished counts in other lymphocyte subsets, including B and Natural Killer (NK) cells. Most screening laboratories may repeat testing internally, refer the newborn for clinical follow-up and additional flow cytometry analysis, or may utilize specific confirmatory approaches for premature or low birth weight (LBW) infants This diversity in follow-up has precluded a facile harmonization of post-screen abnormal results. The Primary Immunodeficiency Treatment Consortium (PIDTC) has developed diagnostic criteria for typical and leaky SCID using analysis of lymphocyte subsets including naïve and memory T cells along with T cell proliferation to PHA [19] (Table 1) These analyses are of utility in assessing other causes of TCL identified by NBS SCID such as variant SCID or idiopathic TCL, syndromes associated with TCL, secondary TCL, and prematurity (Table 1) [20]. Secondary T-cell lymphopenia e.g., Intestinal lymphangiectasia, anasarca, gastroschisis, third-spacing, gastrointestinal atresia, cardiac surgery with/without thymectomy, congenital heart defects, congenital infection with HIV, and neonatal leukemia
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