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

Abstract

To evaluate the diagnostic capability of the T-cell receptor excision circles– (TRECs) based newborn screen (NBS) for severe combined immunodeficiency disease (SCID) in California.The population studied includes all infants born in hospitals in California from 2010 to 2016, with the exception of families opting out for religion.Dried blood spot specimens were obtained from the infants via heel punch for DNA extraction and evaluation of TREC count as a part of the NBS. TREC testing was initially performed at a single facility in California until 2015 and then in regional laboratories across the state starting in 2015, using a new neonatal TREC kit. Threshold values for positive screening results were therefore adjusted after the change of methods. Infants with positive screen results or 2 indeterminate screen results obtained laboratory testing for complete blood count and lymphocyte subsets. Infants with <300 absolute T cells per microliter were referred to SCID medical centers, and those with up to 1500 T cells per microliter were managed by pediatric immunologists. All patients continued to be monitored by their general practitioners for the next 6.5 years.A total of 3 252 156 infants underwent SCID newborn screening from August 2010 to March 2017. A total of 562 infants had abnormal screen results, and 213 infants (1 in 15 300 [95% CI: 1 per 13 500 to 1 per 17 700]) were confirmed to have T-cell lymphopenia (TCL) (<1500 cells per microliter). Fifty cases of SCID (1 per 65 000 births [95% CI: 1 per 51 000 to 1 per 90 000]) were identified with TREC screening. The remaining 162 cases of TCL were due to congenital abnormalities, other primary immunodeficiencies, self-limiting TCL, or idiopathic TCL. Infants who were premature or small for gestational age were more likely to demonstrate positive or indeterminate TREC screening results and subsequently noted to have TCL. Forty-nine of 50 children identified with SCID were referred to centers for further management, with 47 children presenting to medical care before any infectious complication (2 developed infection and rash). Forty-six infants (94%) with SCID received a bone marrow transplant, gene therapy, or enzyme replacement therapy and survived. Two of the 50 SCID patients had delayed diagnosis after toddlerhood and were not identified by the TREC screening. Urgent positive test results requiring immediate call back for lymphocyte screen (<4 TRECs) identified 90% of infants with SCID.TREC screening in California has proven to be highly sensitive and specific in the identification of SCID in newborn infants. The test allows infants with SCID and other TCLs to be identified in a timely manner, allowing for early intervention and treatment of these infants.The study demonstrates that identification of patients with TCL is accurate and shows the benefits of early detection of patients who are likely to have SCID. Early management has led to high survival rates posttreatment, likely because most interventions occurred before serious infection. Similar incidences of disease and outcomes were seen in the first 2 years of TREC NBS in California, (J Allergy Clin Immunol. 2013;132[1]:140–150), thus supporting the long-term reliability of TREC testing and its addition to the NBS panel.