Newborn Screening for Severe Combined Immunodeficiency and T-cell Lymphopenia in California, 2010–2017

Abstract

OBJECTIVES: Newborn screening for severe combined immunodeficiency (SCID) was instituted in California in 2010. In the ensuing 6.5 years, 3 252 156 infants in the state had DNA from dried blood spots assayed for T-cell receptor excision circles (TRECs). Abnormal TREC results were followed-up with liquid blood testing for T-cell abnormalities. We report the performance of the SCID screening program and the outcomes of infants who were identified.METHODS: Data that were reviewed and analyzed included demographics, nursery summaries, TREC and lymphocyte flow-cytometry values, and available follow-up, including clinical and genetic diagnoses, treatments, and outcomes.RESULTS: Infants with clinically significant T-cell lymphopenia (TCL) were successfully identified at a rate of 1 in 15 300 births. Of these, 50 cases of SCID, or 1 in 65 000 births (95% confidence interval 1 in 51 000-1 in 90 000) were found. Prompt treatment led to 94% survival. Infants with non-SCID TCL were also identified, diagnosed and managed, including 4 with complete DiGeorge syndrome who received thymus transplants. Although no cases of typical SCID are known to have been missed, 2 infants with delayed-onset leaky SCID had normal neonatal TREC screens but came to clinical attention at 7 and 23 months of age.CONCLUSIONS: Population-based TREC testing, although unable to detect immune defects in which T cells are present at birth, is effective for identifying SCID and clinically important TCL with high sensitivity and specificity. The experience in California supports the rapid, widespread adoption of SCID newborn screening.

Newborn screening for severe combined immunodeficiency and T‐cell lymphopenia

“…Lack of standardized practices has complicated analysis of aggregate performance data across programs, so available data from California, an ethnically diverse state with the highest number of births, are summarized here . The experience of California alone is larger than the previously generated data from 11 pooled screening programs, and consistent follow‐up practices have facilitated outcome tracking.…”

“…In the 6.5 years between August 15, 2010, and March 31, 2017, California screened 3 252 156 newborns for SCID (Figure ) . Of these, only 562 (1/5800 total births, or <0.2% of births) had non‐normal TREC results requiring liquid blood lymphocyte phenotyping.…”

“…Diagnoses of infants with T cell lymphopaenia ( TCL ) detected by SCID newborn screening, including 50 with SCID (adapted from ref ), 71 with a syndrome in which T cells may be insufficient, 25 with TCL secondary to other neonatal conditions, 33 with preterm birth alone, and 33 idiopathic. Forty percent of the 55 initially idiopathic cases were confirmed to have a syndrome after up to 1 year of follow‐up.…”

ASCIA 2019 Conference Abstracts: Poster 1

“…250K -ENGAGING TEENS AND YOUNG ADULTS WITH SEVERE ALLERGIES Sandra Vale 1,2 , Nyssa Booth 1,3 , Richard Loh 1,2,4 Background: The National Allergy Strategy 250K resources were developed to support to the 250,000 teens and young adults living with severe allergy in Australia. This project aimed to improve the 250K website and increase engagement with teens and young adults living with severe allergies.…”

“…Michael O'Sullivan 1,2,3,4 , Jessica Metcalfe 1,4 , Sandra Vale 2,5,6 , Ian Peters 7,8 , Richard Loh 1,2,6 , Karin Orlemann 8 , Sandra Salter 2 , Debbie Palmer 2,4 , Susan Prescott 1,2,4 Introduction: SmartStartAllergy (SSA) is a novel SMS and smartphonebased application to monitor introduction of allergenic foods and support implementation of Australasian Society of Clinical Immunology and Allergy (ASCIA) Guidelines for Infant Feeding and Allergy Prevention. We describe the SSA methodology, and design and interim results of an ongoing randomised controlled trial (RCT) assessing the effectiveness of SSA in promoting uptake of the ASCIA Guidelines.…”