High Rates of Positive Severe Combined Immunodeficiency Screening Among Newborns with Severe Intestinal Failure

Abstract

AbstractPurposeSevere combined immunodeficiency (SCID) screening by T‐cell receptor excision circles (TREC) has been part of Massachusetts routine newborn screening since 2009. Tetratricopeptide repeat domain 7A gene (TTC7A) mutations responsible for hereditary multiple intestinal atresia with combined immunodeficiency (MIA‐CID) were also recently identified. We reviewed newborn SCID screening among infants with intestinal failure and correlated results with patient characteristics and outcomes.MethodsRecords of infants with severe intestinal failure and available newborn screen results treated at a single center 2009–2016 were reviewed retrospectively. Patients with 1 or more positive SCID screens (<252 TREC copies/μL) were compared with those without positive screens. TREC copies/μL were compared with population norms.ResultsOf 70 included infants, 34% had newborn screens with TREC <252 copies/μL, compared with 0.3% of the general population; TREC levels for the cohort were lower than the general population (p<0.001). Of those with positive screens, 42% had prior or subsequent negative screening, 8% had no further workup, and 50% had flow cytometry showing: severe T‐cell lymphopenia (absolute CD3+ <1500 cells/mcL) in 8, 3 of whom had TTC7A mutation–associated MIA‐CID. Four had CD3+ >1500 cells/mcL. MIA‐CID patients had the lowest serum citrulline in the cohort; 4 of the 8 patients with CD3+ <1500 cells/mcL on flow cytometry had newborn screening notable for severe hypocitrullinemia (<3 μM).ConclusionInfants with intestinal failure have lower TREC copies/μL than the general population; one‐third had levels concerning for SCID, and 11% were diagnosed with severe T‐cell lymphopenia. The clinical implications and etiology of this phenomenon remain unknown, but may be related to hypocitrullinemia.