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Severe combined immune deficiency (SCID) is caused by a wide variety of genetic variants that result in absent or diminished levels of mature and functional T cells. SCID Newborn Screening programs that detect T cell receptor excision circles have resulted in early intervention and improvement in survival rates in infants with SCID but have also identified other conditions with low T cells. These conditions trigger what could be thought of as false positive tests for SCID, but for the most part they do reflect low T cells in conditions other than SCID. The scope of this review is entities other than severe combined immune deficiency that cause low T cell receptor excision circles (TRECs) and are thus identified on newborn screening. Secondary immune deficiencies from prematurity, neonatal medical conditions, hypomorphic or incomplete variants of SCID, transient T cell lymphopenia of infancy, and primary immune deficiencies that do not qualify as SCID are all elaborated. Identification and treatment options for these conditions leading to low TRECs are discussed.
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