Newborn screening for severe combined immunodeficiency; the Wisconsin experience (2008-2011)

Area of Science:

• Immunology
• Pediatrics
• Genetics

Background:

• Severe combined immunodeficiency (SCID) is a critical primary immune deficiency marked by a deficit in naive T cells.
• Timely diagnosis and intervention for SCID significantly reduce mortality rates.
• Newborn screening programs are crucial for early identification of such life-threatening conditions.

Purpose of the Study:

• To evaluate the effectiveness of the T-cell receptor excision circle (TREC) assay in newborn screening for SCID and T-cell lymphopenia.
• To determine the positive predictive value and specificity of the TREC assay in a large infant cohort.
• To assess the impact of early TREC assay screening on the timely initiation of life-saving therapies for SCID.

Main Methods:

• Implementation of newborn screening using the TREC assay in Wisconsin starting in 2008.
• Screening of 207,696 infants for T-cell lymphopenia.
• Analysis of abnormal TREC assay results to confirm T-cell numbers and diagnose SCID or T-cell lymphopenia.

Main Results:

• Out of 207,696 screened infants, 72 had abnormal TREC assays.
• The positive predictive value for T-cell lymphopenia was 45.83%, with a specificity of 99.98%.
• Five infants diagnosed with SCID/severe T-cell lymphopenia were identified and received timely hematopoietic stem cell transplantation or other necessary therapies.

Conclusions:

• The TREC assay is a highly sensitive and specific screening tool for detecting SCID and severe T-cell lymphopenia in newborns.
• Newborn screening with the TREC assay facilitates early diagnosis and treatment, including hematopoietic stem cell transplantation.
• This screening approach significantly improves outcomes for infants with SCID by enabling preemptive treatment before severe infections develop.