ABNORMAL TREC RESULTS ON THE OHIO NEWBORN SCREEN IN CHILDREN WITH CARTILAGE-HAIR HYPOPLASIA

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Introduction While newborn screening (NBS) using T-cell receptor excision circle (TREC) analysis was introduced primarily to screen for severe combined immunodeficiency (SCID), it also identifies T-cell lymphopenia or low naive T-cell numbers due to other etiologies. Cartilage-hair hypoplasia (CHH) is an autosomal recessive disorder caused by mutations in the RMRP gene that result in short limbed skeletal dysplasia and a range of immunologic deficits involving both cellular and humoral immune function. The immune defect can range from minor abnormalities to a SCID phenotype. Methods We analyzed the NBS TREC results performed in Ohio between July 2013 and July 2018. We reviewed the results of the immunologic workup in patients with abnormal TREC results who were later confirmed to have CHH. Results A total of 693,706 unique infants had NBS performed between July 2013 and July 2018, with 192 (0.027%) having abnormal TREC results. Eight infants with abnormal TREC results were diagnosed with CHH. This included 6 cases of non-SCID T-cell lymphopenia and 2 children with SCID phenotypes. In the children with abnormal screening and a diagnosis of CHH, the absolute CD4 lymphocyte counts on initial immunophenotyping ranged from 76 – 757 cells/mm3 (median = 552 cells/mm3). The two CHH patients with SCID received bone marrow transplants. Conclusions CHH is a rare genetic disorder associated with widely varying levels of T-cell lymphopenia ranging from clinically insignificant to SCID. The T-cell lymphopenia may cause an abnormal result on the NBS TREC analysis, allowing for early diagnosis of a significant immunodeficiency and institution of life-saving therapies.