Newborn Screening for Severe Combined Immunodeficiency (SCID)
JAIME GRUBERT, MD
Cincinnati Children’s Hospital Medical Center
RANDALL FISHER, MD and KELLY MAPLES, MD
Eastern Virginia Medical School
It is estimated that as many as 50% of infants with SCID die because of late diagnosis.1 Bone marrow stem cell transplantation performed after diagnosis at birth results in a survival rate greater than 90%.2 Long-term survival in those with diagnosis 3.5 months after birth is only 60% to 70%, as a result of infections acquired before transplantation.2 Currently, there is a strong movement to promote newborn screening for SCID.
Because most newborns with SCID are lymphopenic, a simple screen is a complete blood cell count. Newer methods of screening are now available and include T-cell antigenic marker assay and quantification of T-cell receptor excision circles (TRECs).3,4
To date, the most investigated method is quantification of TRECs by real-time polymerase chain reaction. This can be done using dried blood spots on Guthrie cards. The TREC assay quantifies small pieces of circular DNA that are excised during T-cell receptor editing, which occurs in the thymus. TRECs are at very low levels or absent in peripheral blood of patients with SCID, regardless of genotype. The sensitivity and specificity of absent TRECs is 84% and 97%, respectively; using a cut-off of less than 30 TRECs/mL increases the sensitivity to 100% without changing the specificity. This method also identifies non-SCID cases of immunodeficiency.4
Some have argued that SCID is too rare to be included in newborn screening programs. However, the incidence (1/40,000 to 1/100,000) is comparable to that of galactosemia and biotinidase deficiency (1/60,000 and 1/80,000, respectively). In addition, after start-up, the cost is only $5.50 per test.4
Pilot programs to test the feasibility of screening all newborns for SCID are under way. Wisconsin has been using universal testing since 2008. Trials have been ongoing since 2009 in Massachusetts and Texas and are about to start in New Mexico and Arizona. SCID is the first disease to be recommended by the Advisory Committee on Heritable Disorders in Newborns and Children to the US Department of Health and Human Services for inclusion on the federal core newborn screening panel. It will be several more years before SCID screening is implemented in all 50 states.