A Retrospective Chart Review of Infants Referred for Abnormal TREC on Newborn Screen

RATIONALE: In 2010, the New York State Newborn Screening Program added the T-cell receptor excision circle (TREC) assay to screen for severe combined immunodeficiency (SCID). We hypothesized that average TREC number is associated with primary immunodeficiency and that confirmatory testing options to exclude primary immunodeficiency would differ in time to result.

METHODS: This retrospective chart review collected demographic, average TREC value, and follow-up testing data for 199 infants referred to our institution for abnormal TREC on New York State Newborn Screening. Statistical analysis included analysis of variance, logistic regression model, and linear mixed model.

RESULTS: Infants were stratified as primary immunodeficiency (27%), no primary immunodeficiency (62%), or unknown immune status (11%) through a diagnostic algorithm. Primary immunodeficiency included SCID (3), DiGeorge (4), T or B cell lymphopenia (43), and other syndromes (4). There was a difference in the average TREC number between those with SCID or DiGeorge (45) and those with no primary immunodeficiency (80) (p-value 0.04). In infants with an average TREC greater than 160, there was 100% sensitivity in predicting no primary immunodeficiency. For infants without primary immunodeficiency, there was a difference in age at result of first normal TREC value (27±17), lymphocyte subsets (49±49), and mitogen study (81±85) after the initial abnormal TREC value (p-value <0.0001).

CONCLUSIONS: For infants with an abnormal TREC assay on New York State Newborn Screen, the infants can be risk stratified by average TREC. In these infants, confirmatory testing with repeat TREC assay and lymphocyte subsets excludes primary immunodeficiency earlier than mitogen studies.