Newborn Screening for Severe Combined Immunodeficiency in 11 Screening Programs in the United States

Abstract

IMPORTANCE Newborn screening for severe combined immunodeficiency (SCID) using assays to detect T-cell receptor excision circles (TRECs) began in Wisconsin in 2008, and SCID was added to the national recommended uniform panel for newborn screened disorders in 2010. Currently 23 states, the District of Columbia, and the Navajo Nation conduct population-wide newborn screening for SCID. The incidence of SCID is estimated at 1 in 100 000 births. OBJECTIVES To present data from a spectrum of SCID newborn screening programs, establish population-based incidence for SCID and other conditions with T-cell lymphopenia, and document early institution of effective treatments. DESIGN Epidemiological and retrospective observational study. SETTING Representatives in states conducting SCID newborn screening were invited to submit their SCID screening algorithms, test performance data, and deidentified clinical and laboratory information regarding infants screened and cases with nonnormal results. Infants born from the start of each participating program from January 2008 through the most recent evaluable date prior to July 2013 were included. Representatives from 10 states plus the Navajo Area Indian Health Service contributed data from 3 030 083 newborns screened with a TREC test. MAIN OUTCOMES AND MEASURES Infants with SCID and other diagnoses of T-cell lymphopenia were classified. Incidence and, where possible, etiologies were determined. Interventions and survival were tracked. RESULTS Screening detected 52 cases of typical SCID, leaky SCID, and Omenn syndrome, affecting 1 in 58 000 infants (95%CI, 1/46 000-1/80 000). Survival of SCID-affected infants through their diagnosis and immune reconstitution was 87%(45/52), 92%(45/49) for infants who received transplantation, enzyme replacement, and/or gene therapy. Additional interventions for SCID and non-SCID T-cell lymphopenia included immunoglobulin infusions, preventive antibiotics, and avoidance of live vaccines. Variations in definitions and follow-up practices influenced the rates of detection of non-SCID T-cell lymphopenia. CONCLUSIONS AND RELEVANCE Newborn screening in 11 programs in the United States identified SCID in 1 in 58 000 infants, with high survival. The usefulness of detection of non-SCID T-cell lymphopenias by the same screening remains to be determined.

Newborn Screening for Primary Immune Deficiencies with a TREC/KREC/ACTB Triplex Assay—A Three-Year Pilot Study in Sweden

“…Newborn screening for primary immune deficiencies by TREC analysis is included in almost all programs in the United States, as well as in some other countries [7,9,[16][17][18][19]. With this methodology, patients with defects in the production of T-cells can be identified, but isolated B-cell defects escape detection.…”

Newborn Screening for Severe Combined Immunodeficiency in Israel

“…If untreated, infants with SCID succumb early in life to severe and recurrent infections [8]. Recent estimates, based on the results of American SCID neonatal screening, indicate an SCID incidence of 1.7:100,000 in the general population [9], but it is substantially higher in some populations. In the aforementioned Broides et al study, the overall incidence of SCID/CID in the Bedouin population of southern Israel was 18.3:100,000 [5].…”

Long-term outcome of hematopoietic stem cell transplantation for IL2RG/JAK3 SCID: a cohort report

“…Defects in the interleukin-2 g-chain receptor (IL2RG) are most common. 1 Less common defects in JAK3 are downstream of IL2RG signaling: both forms present with a T-lymphocyte-negative, B-lymphocyte-positive, NK-cell-negative immunophenotype. B lymphocytes are present, but intrinsic signaling defects render them nonfunctional.…”