Severe combined immunodeficiency (SCID) is a diverse group of rare genetic conditions that primarily affect newborns and infants. These disorders are attributable to defects in adaptive immunity and are largely the result of genetic mutations that lead to impaired T cell function. Because the majority of neonates affected by the disease show no symptoms at birth, newborn screening has been recognized as an effective method to detect SCID before later diagnosis in infancy.1,2

In a recent study published in Pediatrics, George S Amatuni, BS, of the department of pediatrics at the University of California, San Francisco, and colleagues reported findings from a universal newborn screening program for SCID and T-cell lymphopenia that took place in California from 2010 to 2017. In addition, the team provided recommendations for the use of T-cell receptor excision circle (TREC) testing to detect these disorders in newborns.

Jennifer M Puck, MD, of the department of pediatrics at the University of California, San Francisco, and coauthor of the study, told Hematology Advisor, “SCID is an immune deficiency, which is not the same as other hematologic diseases. SCID newborn screening has been very successful [in] identifying affected infants whose families and doctors [may] have never heard of anyone with the [disorder].”

Pathogenesis of SCID and T-Cell Lymphopenia

Individuals with deficiencies in T lymphocyte function are susceptible to many severe infections, both common and opportunistic, that can be caused by various bacterial, viral, and fungal pathogens. Researchers have identified specific mutations in known SCID genes that result in impaired immune function. As a result, early diagnosis of SCID and other T-cell abnormalities in newborns is essential to prevent life-threatening infectious complications.

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With respect to diagnosis, Donald B Kohn, MD, of the department of pediatrics at the University of California in Los Angeles, who is also a coauthor of the study, told Hematology Advisor, “One point [for] hematologists to remember [is] to review the absolute lymphocyte counts when [ordering] complete blood counts, as well as the absolute neutrophil counts to which [hematologists] are often more attuned.”

The Universal Screening Program in California

The state of California launched a population-based universal newborn screening program for SCID in 2010. The screening test used a TREC assay, which measures distinct DNA biomarkers of T-cell development through polymerase chain reaction technology. If an abnormal result was reported, further testing was completed using liquid blood phenotyping to analyze specific T-cell markers for other non-SCID disorders, such as T-cell lymphopenia. Prompt diagnosis and treatment of these non-SCID disorders is also essential to reducing the risk for severe infections.