PURPOSE OF THE STUDY.
To assess the results of a spectrum of state-based newborn screening programs using the T-cell receptor excision (TREC) testing approach to develop more accurate population-based incidence of severe combined immunodeficiency (SCID) and other conditions associated with T-cell lymphopenia and document the effectiveness of early intervention in those newborns found to have a significant immunologic abnormality.
Cumulative TREC newborn screening data were evaluated from 10 states plus the Navajo Nation involving ∼3 million newborns.
This was an epidemiologic and retrospective observational study based on states invited to submit SCID screening algorithms, test performance data, and deidentified clinical and laboratory information regarding infants screened and cases with nonnormal results. The data evaluated were collected from January 2008 through June 2013 (intervals for each program varied based on the actual initiation date of the program).
The newborn screening programs detected 52 infants with typical SCID (n = 42, 81%) or leaky SCID/Omenn syndrome (n = 10, 19%), generating an overall incidence of SCID at 1 in 58 000 infants. No cases of SCID were missed using the TREC-based newborn screening approach. The overall survival of SCID-affected infants was 87% (45 of 52) and survival for those who received hematopoietic stem cell transplantation, adenosine deaminase enzyme replacement, or gene therapy was 92% (45 of 49). The distribution of genetic defects associated with SCID in this nonbiased data set demonstrated that the incidence of X-linked SCID is less frequent than previous studies suggested (19% of all cases), whereas autosomal recessive SCID due to RAG1 defects (15%), interleukin-7 receptor defect (12%), and adenosine deaminase deficiency (11%) were more common. There were also 117 cases of T-cell lymphopenia attributable to other causes with the most common being congenital heart disease, other congenital anomalies, vascular leakage and hydrops, gastrointestinal anomalies, and 4 neonatal leukemias.
This study strengthens the case for SCID newborn screening because the incidence of SCID is higher than previously predicted and well within the range of disorders that qualify for newborn screening based on frequency. In addition, the favorable outcome from early intervention in SCID is supported by the treatment results observed in the management of SCID infants identified in this multistate newborn screening program. The TREC assay has proven to be excellent for detecting disorders associated with defected T-cell production as well as disorders with diminished circulating T cells.
This report further expands a previous report that was based exclusively on TREC newborn screening for SCID in California. The frequency of SCID in this initial report was confirmed in this larger study involving multiple states (1:58 000). The success of this program has resulted in additional states adding the TREC assay to their newborn screening program such that currently 90% of all newborns in the United States are now screened for SCID and other severe T-cell immunodeficiencies. In addition to the clear advantage of early intervention that comes with newborn disease detection, this screening program allows protective measures to be put in place, such as withholding live viral vaccines and avoidance of day-care settings until definitive therapy can be initiated. There remain a small number of newborns with abnormal TREC screening results and T-cell lymphopenia who do not appear to have a defined primary immunodeficiency, and the ultimate outcome in these infants remains to be clarified. It would be desirable to develop a more consistent approach to SCID newborn screening using the TREC assay and criteria for follow-up that focuses on preventing unnecessary referral to diminish the burden of heightened parental anxiety and the additional cost.
- Copyright © 2015 by the American Academy of Pediatrics