Development of a routine newborn screening protocol for severe combined immunodeficiency

Area of Science:

• Immunology
• Genetics
• Neonatal Screening

Background:

• Severe Combined Immunodeficiency (SCID) is a life-threatening genetic disorder characterized by absent functional T and B cells.
• Infants with SCID face high mortality rates due to severe infections within the first year of life without timely diagnosis and treatment.

Purpose of the Study:

• To assess the feasibility of detecting SCID in newborns by quantifying T-cell receptor excision circles (TRECs).
• To utilize dried blood spots (DBSs) on newborn screening (NBS) cards for TREC analysis.

Main Methods:

• DNA extraction from deidentified DBSs on NBS cards.
• Real-time quantitative PCR (RT-qPCR) employed to determine TREC quantities.
• Inclusion of positive controls, including a SCID patient sample and T-cell depleted specimens.

Main Results:

• Analysis of 5766 DBSs yielded mean and median TREC counts of 827 and 708 per punch, respectively.
• Ten samples initially failed TREC amplification but mostly normalized upon retesting.
• No TRECs were detected in SCID or T-cell depleted samples, confirming assay specificity.

Conclusions:

• RT-qPCR quantification of TRECs from newborn DBSs is a highly sensitive and specific screening method for SCID.
• This TREC-based assay is currently implemented for routine SCID screening in Wisconsin infants.