Implementing routine testing for severe combined immunodeficiency within Wisconsin's newborn screening program

Abstract

Severe combined immunodeficiency (SCID) is the result of genetic defects that impair normal T-cell development. SCID babies typically appear normal at birth, but acquire multiple life-threatening infections within a few months. Early diagnosis and treatment with a bone-marrow transplant markedly improves long-term outcomes. On January 1, 2008, the newborn screening (NBS) program in Wisconsin became the first in the world to routinely test all newborns for SCID. A realtime quantitative polymerase chain reaction assay measures T-cell receptor excision circles (TRECs), which are formed during the maturation of normal T-cells. A lack or very low number of TRECs is consistent with T-cell lymphopenia. The development and validation of the TREC assay and the results of the first year of screening have been published. This article describes the process used to add SCID to the NBS panel, the establishment of follow-up capacity, and the integration of SCID screening into routine NBS workflows. The development of this expanded NBS program is described so that other states might benefit from the processes used in Wisconsin.

Figure 1.

Graphic representation of SCID-screening method used by the Wisconsin NBS Program^a

Figure 2.

Calibrator curve of serially diluted plasmids containing a known number of TRECs (solid squares) and 82 unknown samples^a

Figure 4.

Results of initial RT-qPCR TREC assay conducted by the Wisconsin NBS Program on 5,766 NBS cards during the 2007 SCID-screening pilot study^a,b