Screening for Severe Combined Immunodeficiency on the Ohio Newborn Screen Using TREC Analysis: Experience from the First Four Years

RATIONALE: Newborn screening (NBS) for severe combined immunodeficiency (SCID) using T cell receptor excision circle (TREC) analysis was initiated in order to promote early diagnosis and improve outcomes in infants with this life-threatening condition. In July 2013, TREC analysis was added to the Ohio NBS. We report Ohio’s 4 year experience.

METHODS: DNA was extracted from NBS specimens and TREC sequences were amplified using real-time PCR. Prior to implementing statewide screening, amplification values were established based on samples from infants previously diagnosed with SCID. Algorithms for triaging infants with an abnormal NBS were developed factoring in age of gestation and NICU status.

RESULTS: Over the first 4 years of testing, 551,653 infants were screened. A total of 168 infants had an abnormal TREC result on initial NBS. Of these infants, 107 had normal repeat screens, 36 received immediate further diagnostic evaluation, 24 expired, and 1 was lost to follow-up. Seven infants receiving further testing were diagnosed with SCID. Fifteen had syndromes associated with other T cell lymphopenia (TCL) and 10 had TCL of unknown etiology. Based on our established algorithm, only 0.03% of infants had an abnormal NBS and <0.01% of cases required further diagnostic evaluation. To our knowledge, no known SCID cases have been missed.

CONCLUSIONS: Newborn screening for SCID using analysis of TREC amplification is an effective public health intervention to promote early diagnosis and management of SCID. Since implementation, our screening algorithm has proven to have a high sensitivity for detecting SCID while maintaining a low rate of false positives.