Assay of T cell receptor excision circles (TRECs) in dried blood spots (DBS) obtained at birth permits population-based newborn screening (NBS) for severe combined immunodeficiency (SCID).
To report the first 2 years of TREC NBS in California.
Since August 2010, California has conducted SCID newborn screening. A high-throughput TREC qPCR assay using DNA isolated from routine DBS was developed. Samples with initial low TREC values had repeat DNA isolation with qPCR for TRECs and a genomic control, and immunophenotyping was performed within the screening program for infants with incomplete or abnormal results. Outcomes were tracked.
Of 993,724 infants screened, 50 (1/19,900; 0.005%) had significant T cell lymphopenia. Fifteen (1/66,250) required hematopoietic cell or thymus transplantation or gene therapy; these infants had typical SCID (11), leaky SCID or Omenn syndrome (3), or complete DiGeorge syndrome (1). Survival to date in this group is 93%. Other T lymphopenic infants had variant SCID or combined immunodeficiency (6), genetic syndromes associated with T cell impairment (12), secondary T lymphopenia (9) or preterm birth (8). All T lymphopenic infants avoided live vaccines and received appropriate interventions to prevent infections. TREC test specificity was excellent: only 0.08% of infants required a second test and 0.016% required lymphocyte phenotyping by flow cytometry.
TREC NBS in California has achieved early diagnosis of SCID and other conditions with T lymphopenia, facilitating management and optimizing outcomes. Furthermore, NBS has revealed the incidence, causes and follow-up of T lymphopenia in a large, diverse population.