Ten Years of Newborn Screening for Severe Combined Immunodeficiency (SCID) in Massachusetts

Author Department

Pediatrics

Document Type

Article, Peer-reviewed

Publication Date

2-2021

Abstract

Background: Massachusetts began newborn screening (NBS) for severe combined immunodeficiency (SCID) using measurement of T cell receptor excision circles (TRECs) from dried blood spots.

Objective: We describe developments and outcomes from the first 10 years of this program (Feb 1 2009-Jan 31 2019).

Methods: TREC values, diagnostic, and outcome data from all patients screened for SCID were evaluated.

Results: NBS of 720,038 infants prompted immunologic evaluation of 237 (0.03%). 9/237 were diagnosed with SCID/leaky SCID (4% of referrals vs 0.001% general population). Another 7 were diagnosed with other combined immunodeficiencies, and 3 with athymia. SCID/leaky SCID incidence was ∼1 in 80,000, while ∼1 in 51,000 had severe T cell lymphopenia for which definitive treatment was indicated. All patients with SCID/leaky SCID underwent hematopoietic cell transplant or gene therapy with 100% survival. One patient with athymia underwent successful thymus transplant. No known cases of SCID were missed. Compared to outcomes from the 10 years prior to SCID NBS, survival was higher (9/9 vs 4/7), likely due to a lower rate of infection before treatment.

Conclusions: Our data support a single NBS testing-and-referral algorithm for all gestational ages. Despite lower median TREC values in premature infants, the majority for all ages are well above the TREC cutoff and the algorithm, which selects urgent (undetectable TREC) and repeatedly abnormal TREC, minimizes referral. We also found that low naïve T cell percentage is associated with a higher risk of SCID/CID, demonstrating the utility of memory/naïve T cell phenotyping as part of follow-up flow cytometry.

Keywords: Newborn screening (NBS); SCID; TREC; athymia; hematopoietic cell transplant (HCT); prematurity.

PMID

33607339

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