Abstract
The implementation of severe combined immunodeficiency (SCID) newborn screening has played a pivotal role in identifying these patients early in life as well as detecting various milder forms of T cell lymphopenia (TCL). In this study we reviewed the diagnostic and clinical outcomes, and interesting immunology findings of term infants referred to a tertiary care center with abnormal newborn SCID screens over a 6-year period. Key findings included a 33% incidence of non-SCID TCL including infants with novel variants in FOXN1, TBX1, MYSM1, POLD1, and CD3E; 57% positivity rate of newborn SCID screening among infants with DiGeorge syndrome; and earlier diagnosis and improved transplant outcomes for SCID in infants diagnosed after compared to before implementation of routine screening. Our study is unique in terms of the extensive laboratory workup of abnormal SCID screens including lymphocyte subsets, measurement of thymic output (TREC and CD4TE), and lymphocyte proliferation to mitogens in nearly all infants. These data allowed us to observe a stronger positive correlation of the absolute CD3 count with CD4RTE than with TREC copies, and a weak positive correlation between CD4RTE and TREC copies. Finally, we did not observe a correlation between risk of TCL and history of prenatal or perinatal complications or low birth weight. Our study demonstrated SCID newborn screening improves disease outcomes, particularly in typical SCID, and allows early detection and discovery of novel variants of certain TCL-associated genetic conditions.
Highlights
Severe combined immunodeficiency (SCID) comprises a broad group of genetic disorders of the adaptive immune system in which T cell, and sometimes B and NK cell, development and function are impaired
72% were male, 62% were Caucasian, and 33% were African-American. 51% were from Missouri and the rest from Illinois. 3% were premature but had persistently abnormal newborn SCID screening at 36 weeks corrected gestational age or later
Prior to January 2019, when Missouri’s cycle threshold cutoff for a positive SCID screen was increased, this false positive rate was slightly higher at 69%. 33% of infants had non-SCID T cell lymphopenia (TCL), and 6% had typical SCID (N=6), leaky SCID (N=3) or complete DiGeorge phenotype (N=1)
Summary
Severe combined immunodeficiency (SCID) comprises a broad group of genetic disorders of the adaptive immune system in which T cell, and sometimes B and NK cell, development and function are impaired. In the United States screening was first implemented in Wisconsin in 2008, and in all 50 states by 2018 This has allowed for earlier diagnosis and treatment, typically with hematopoietic stem cell transplant, gene therapy, or enzyme replacement, and has led to improved survival of infants with SCID (2–6). These outcomes are highlighted in a study from the Primary Immune Deficiency Treatment Consortium which found 94% survival among infants who were transplanted by 3.5 months age, versus 50% survival among those who had active infection and were transplanted later than 3.5 months age (7).
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