PURPOSE OF THE STUDY.
Severe combined immunodeficiency (SCID) is a life-threatening disease of infants that is curable with hematopoietic cell transplantation if detected early, whereas the outcome is less favorable if treatment is delayed. The study evaluated outcomes of a screening program in Wisconsin.
Newborns in Wisconsin over a 3-year period.
Population-based screening for SCID by using the T-cell receptor excision circle (TREC) assay applied to samples obtained from routine newborn screening (Guthrie) cards has been underway in the state of Wisconsin since 2008.
Five infants with SCID or other forms of severe T-cell lymphopenia (TCL) have been detected out of a total of 207 696 infants screened between January 1, 2008, and December 31, 2010. Based on these data, the specificity of this screening assay is 99.98% with a false-positive rate of 0.018%. In addition, the positive predictive value of this test as applied for identifying a severe TCL due to any cause was 45.83%. Among 9 infants without other secondary causes for the TCL, 5 had reversible TCL, and 4 had 22q11.2 microdeletion (DiGeorge) syndrome. Importantly, it appears that no infants with SCID have been missed during this screening period.
TREC assay screening as part of routine newborn screening detects infants with severe TCL in a cost-effective fashion and should be adopted as a part of routine newborn screening as currently recommended by the US Department of Health and Human Services.
This report provides the cumulative experience of newborn screening by using the TREC assay over a 3-year period in Wisconsin, proving that it is an effective means of identifying newborns with severe TCL associated with immune deficiencies including SCID and complete DiGeorge syndrome. Importantly, this experience also proved that the TREC assay is unreliable in premature infants such that their current practice is to repeat the TREC assay until an infant reaches an adjusted gestational age of 37 weeks at which time it is viewed as reliable. One clear conclusion from these data is that an infant with severe TCL identified by an abnormal TREC assay should undergo a complete immunologic evaluation managed by an experienced clinical immunologist. Another unanticipated finding from this experience is the fact that there are rare newborns with TCL but normal T-cell function, and as more of these infants are identified it will become clearer as to how they should best be managed. It should be noted that the results of an abnormal TREC assay are available early enough to prevent immunizations with live viral vaccines and exposure to unirradiated blood products until the immune status of the infant is clarified, a situation that should prevent unnecessary complications from these agents.
- Copyright © 2012 by the American Academy of Pediatrics