Statewide newborn screening for severe T-cell lymphopenia.

Area of Science:

• Immunology
• Genetics
• Neonatal screening

Background:

• Profound T-cell deficiency in newborns can lead to increased mortality.
• Newborn blood screening (NBS) offers a potential method for early identification of at-risk infants.
• Early detection of T-cell lymphopenia is crucial for timely intervention and improved outcomes.

Purpose of the Study:

• To evaluate the efficacy of quantifying T-cell receptor excision circles (TRECs) via real-time quantitative polymerase chain reaction (qPCR) on dried blood spots.
• To determine if TREC quantitation on NBS cards can reliably detect infants with T-cell lymphopenia within a large-scale, statewide program.
• To assess the feasibility of integrating TREC analysis into existing newborn screening protocols.

Main Methods:

• A statewide screening program in Wisconsin analyzed TREC levels in approximately 71,000 infants born between January 1 and December 31, 2008.
• DNA was extracted from dried blood spots on NBS cards, and TREC numbers were quantified using real-time qPCR.
• Infants with TREC values below 25/microL underwent confirmatory testing using flow cytometry to enumerate T cells, with clinical evaluation by an immunologist for those diagnosed with T-cell lymphopenia.

Main Results:

• The TREC assay identified 17 infants with abnormal TREC values (< 25/microL) among the 71,000 screened.
• Flow cytometry confirmed T-cell lymphopenia in 8 of these infants.
• Diagnoses included DiGeorge syndrome, idiopathic T-cell lymphopenia, extravascular extravasation of lymphocytes, and a Rac2 mutation, with one infant successfully treated via cord blood transplantation.

Conclusions:

• The TREC assay, performed on standard NBS cards, effectively identified infants with T-cell lymphopenia in a real-world, statewide screening setting.
• This method demonstrates the potential for reducing mortality associated with profound T-cell deficiencies through early detection.
• Quantitating TRECs is a viable strategy for enhancing newborn screening protocols to include T-cell lymphopenia detection.