Baby feet.

A condition in infants that leads to severe infection and sometimes death if untreated occurs in 1 in 58,000 births, higher than previously estimated.

The first multi-state report of severe combined immunodeficiency (SCID) in newborns underscores the importance of screening efforts to detect this potentially life-threatening condition. The results were published in the August 20 issue of the Journal of the American Medical Association.

Research conducted by Antonia Kwan, PhD, MRCPCH, of the University of California, San Francisco, and her colleagues analyzed more than 3 million babies who were screened for SCID with a T-cell receptor excision circle (TREC) test in 10 states and the Navajo Nation.

The programs detected 52 cases of SCID, yielding an overall incidence of 1 in 58,000 births. This compares to previous estimates of 1 in 100,000 births. “SCID is a disorder that, when identified early and treated, can save lives. But until this study, the medical community had imprecise estimates of the prevalence of the disorder,” observes Stanley J. Naides, MD, a medical director with Quest Diagnostics, and one of the study’s researchers.

“This data shows that the disorder is about twice as prevalent as had previously been estimated,” adds Naides. Of the infants diagnosed with SCID, 81% had typical SCID, whereas 19% had leaky SCID. Referral centers that treat SCID have reported that about 50% of cases are due to mutations in the X chromosome-linked IL2RG gene, but the researchers found this mutation accounted for just 19% of cases across the 11 programs.

Incidence rates didn’t vary significantly from state to state, although they were notably high in the Navajo Nation (1:3,500). This population is known to have a mutation in DCLRE1C, which encodes a DNA repair protein, leading to SCID. “Although each public health program was designed a bit differently, all were successful at detecting SCID, and no cases of SCID were missed,” Kwan said in a statement.

Overall, the findings show that this condition has been underdiagnosed in babies with fatal infections, pointing to a need to conduct additional screening.

SCID since 2010 has been a part of the Department of Health and Human Services’ Recommended Uniform Screening Panel. Currently, just 23 states, the District of Columbia, and the Navajo Nation use a DNA test to screen about two-thirds of all U.S.-born infants for SCID.

A high survival rate exists among SCID-diagnosed babies who receive immunity-restoring therapies such as hematopoietic cell transplants, gene correction of IL2RG and ADA defects, or adenosine deaminase enzyme injection therapy. More than 90% of the babies who were treated survived.

From the lab practice standpoint, the researchers found that the participating newborn screening programs followed similar testing protocols of screening with a TREC test, followed by flow cytometry to enumerate T, B, and NK cells, along with naïve and memory phenotype T cells. However, the programs used different TREC cutoffs for instigating flow cytometry, and they also defined T-cell lymphopenia differently. For example, six programs defined significant T-cell lymphopenia as T-cell count <1,500/µL, whereas four used a cutoff of <2,500/µL, and one left the definition in the hands of individual immunologists. This led to varying false-positive rates, ranging from 0% to 82%.

The researchers called this lack of uniformity in assay methodology and rules a “major limitation” of their study.