Newborn Screening Identifies SCID and T-Cell Lymphopenia

By Will Boggs MD

February 05, 2019

NEW YORK (Reuters Health) - Newborn screening of DNA from dried blood spots identifies infants with severe combined immunodeficiency (SCID) and clinically important non-SCID T-cell lymphopenia, researchers report.

Population-based newborn screening is the only strategy for identifying all infants with SCID early enough to provide treatment before infectious complications ensue. California instituted population-wide screening for SCID in 2010, and currently all 50 states in the U.S., plus the District of Columbia and Puerto Rico, and an increasing number of countries have adopted universal newborn screening for SCID.

The SCID newborn screening test is based on the detection of T-cell receptor excision circles (TRECs), DNA markers of normal T lymphopoiesis that can be measured by PCR using dried blood spots routinely obtained from newborns by heel stick.

Dr. Jennifer M. Puck from University of California, San Francisco and Benioff Children's Hospital and colleagues report the experience and outcomes of the first 6.5 years of screening >3.25 million newborns for SCID in California, in a January 25th Pediatrics online report.

During this time, TREC screening identified 50 cases of SCID (1 per 65,000 births). Among the cases of non-SCID T-cell lymphopenia, there were 72 categorized as congenital syndromes (most commonly DiGeorge syndrome, in 47 infants), 25 resulting from another condition and resolving once that condition was corrected, 33 related to preterm birth alone and resolving if the infant survived, and 33 idiopathic cases.

Of the 50 infants with SCID, 49 were immediately hospitalized for treatment with allogeneic hematopoietic cell transplant from a suitably matched healthy donor, autologous corrected cell gene therapy, or enzyme replacement therapy. The other infant born to a foreign visitor left the U.S. before receiving further evaluation or treatment.

Survival of patients with SCID was 94% at 1 to 8 years of age, and 31 of the 46 surviving children (67%) had fully reconstituted B- as well as T-cell immunity and no longer required IgG supplementation.

Screening missed no known cases of typical SCID, but two infants with delayed-onset leaky SCID resulting from missense defects in the ADA and IL2RG genes had normal TREC newborn screening and did not come to clinical attention until 7 and 23 months of age.

"The experience in California supports the rapid, widespread adoption of SCID newborn screening," the researchers conclude.

Dr. John M. Routes from Children's Hospital of Wisconsin and the Medical College of Wisconsin, in Milwaukee, who has extensively researched newborn screening for SCID, told Reuters Health by email, "The paper reinforces what we already know: the TREC assay is great to pick up SCID, (but) we will miss other combined immunodeficiencies if there are enough naïve T cells present in the peripheral blood."

"Early diagnosis improves outcome by transplantation," he said.

Dr. Puck did not respond to a request for comments.


Pediatrics 2019.