Newborn Screening for Severe Combined Immunodeficiency

The most recent disorder that has been recommended for addition to all US newborn screening (NBS) programs is severe combined immunodeficiency (SCID). SCID is actually a group of at least 14 primary immunodeficiencies which affect the individual’s immune system, making it impossible for them to adequately fight off infections. A baby with SCID who does not receive treatment rarely survives the first year of life, being unable to clear repeated and massive infections. Everyone probably remembers the story of the “Bubble Boy” who survived 12 years in a completely sterile environment. The “Bubble Boy” had SCID.

Screening newborns for this disorder would seem like a no-brainer; however, because SCID is actually many different primary immunodeficiencies, finding a screening test that would pick up all or the majority of them has been problematic. In recent years, people began looking at one of the hallmarks of all SCID, a lack or very low number of functional T-cells.

During maturation in the thymus, T-cells undergo gene rearrangement, and during this process small extra-chromosomal circles of DNA are created as the segments of DNA are clipped out of the gene. These small DNA circles are call T-cell receptor excision circles, or TREC. In 1998, Douek et al (1) developed a PCR assay to quantify TREC as a measure of thymic function. When that assay was published, researchers began wondering whether there would be any TREC produced in a disorder like SCID with no functional T-cells. Very quickly the TREC PCR assay was adapted to measure the presence of TREC in dried blood spots, and several papers showed that in SCID individuals, essentially no TREC are produced. Thus the PCR assay for TREC became a viable screening test for SCID in newborns.

Currently 18 States are either already screening for SCID or are in the process of adding SCID screening to their NBS. There is a ways to go before this screening becomes part of all programs in the US, however, given the morbidity and mortality associated with the disease and the availability of a test, it’s hopefully only a matter of time.

1. Douek DC, McFarland RD, Keiser PH, Gage EA, Massey JM, Haynes BF, et al.  Changes in thymic function with age and during the treatment of HIV infection. 1998. Nature. 396:690-695.

 

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-Patti Jones PhD, DABCC, FACB, is the Clinical Director of the Chemistry and Metabolic Disease Laboratories at Children’s Medical Center in Dallas, TX and a Professor of Pathology at University of Texas Southwestern Medical Center in Dallas.

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