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Abnormal Newborn Screening Follow-up for Severe Combined Immunodeficiency in an Amish Cohort with Cartilage-Hair Hypoplasia

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Abstract

Cartilage-hair hypoplasia (CHH) is an autosomal recessive, short limb skeletal dysplasia with a variable immunologic phenotype. The spectrum of immune function ranges from clinically normal to severe combined immunodeficiency (SCID). Multiple studies have shown that abnormal immune parameters may not predict severe outcomes. Newborn screening (NBS) using T cell receptor excision circle (TREC) assay can now effectively identify infants with severe T cell deficiency who are at risk for SCID. NBS has allowed for cost-effective identification of patients with SCID and improved outcomes with hematopoietic stem cell transplant (HSCT). Ohio reports two abnormal TREC results: decreased and absent TREC. This study evaluated the laboratory and clinical differences in eight Amish patients with CHH with an abnormal TREC result on the NBS. There were four patients with absent TREC and four patients with decreased TREC. The absent TREC patients had lower CD3, CD4, naïve CD4, CD8 cells, and phytohemagglutinin (PHA)-induced lymphocyte proliferation. Three patients with absent TREC were diagnosed with SCID and two underwent successful HSCT. Patients with absent TREC experienced more CHH-related morbidity including anemia requiring transfusion, Hirschsprung’s disease, and failure to thrive. No patients with decreased TREC required HSCT. Our study indicates that CHH patients with absent TREC tend to have more severe immunological and clinical phenotype than patients with decreased TREC. Confirmation of these trends in a larger group would guide providers and parents in a timely referral for HSCT, or cost-effective surveillance monitoring of children with a life-threatening illness.

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Authors and Affiliations

  1. New Leaf Center Clinic for Special Children, 15988 Chestnut, Mt Eaton, OH, 44659, USA

    Ethan M. Scott & Olivia K. Wenger

  2. Department of Pediatrics, Akron Children’s Hospital, 214 W Bowery St, Akron, OH, 44308, USA

    Ethan M. Scott, Jinzhu Li, Eric D. Robinette & Olivia K. Wenger

  3. Division of Bone Marrow Transplantation and Immune Deficiency, Children’s Hospital Medical Center, Cincinnati, Ohio - 3333 Burnet Ave, Cincinnati, OH, 45229, USA

    Sharat Chandra

  4. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio- 3333 Burnet Ave, Cincinnati, OH, 45229, USA

    Sharat Chandra

  5. Akron Children’s Hospital, Rebecca D Considine Research Institute, 214 W Bowery St, Akron, OH, 44308, USA

    Miraides F. Brown

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  1. Ethan M. Scott
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Correspondence to Ethan M. Scott.

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Scott, E.M., Chandra, S., Li, J. et al. Abnormal Newborn Screening Follow-up for Severe Combined Immunodeficiency in an Amish Cohort with Cartilage-Hair Hypoplasia. J Clin Immunol 40, 321–328 (2020). https://doi.org/10.1007/s10875-019-00739-9

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  • DOI: https://doi.org/10.1007/s10875-019-00739-9

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