New Leaf Center Clinic for Special Children, 15988 Chestnut, Mt Eaton, OH, 44659, USA.
Department of Pediatrics, Akron Children's Hospital, 214 W Bowery St, Akron, OH, 44308, USA.
J Clin Immunol. 2020 Feb;40(2):321-328. doi: 10.1007/s10875-019-00739-9. Epub 2020 Jan 6.
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.
软骨-毛发发育不全（CHH）是一种常染色体隐性、短肢骨骼发育不良疾病，具有可变的免疫表型。免疫功能谱从临床正常到严重联合免疫缺陷（SCID）不等。多项研究表明，异常免疫参数可能无法预测严重后果。现在，使用 T 细胞受体切除环（TREC）检测的新生儿筛查（NBS）可以有效地识别出有发生 SCID 风险的严重 T 细胞缺陷婴儿。NBS 允许以具有成本效益的方式识别出患有 SCID 的患者，并通过造血干细胞移植（HSCT）改善其预后。俄亥俄州报告了两种异常 TREC 结果：减少和缺失 TREC。本研究评估了 NBS 上出现异常 TREC 结果的 8 名阿米什 CHH 患者的实验室和临床差异。有 4 名患者 TREC 缺失，4 名患者 TREC 减少。TREC 缺失的患者 CD3、CD4、幼稚 CD4、CD8 细胞和植物血凝素（PHA）诱导的淋巴细胞增殖较低。3 名 TREC 缺失患者被诊断为 SCID，其中 2 名患者接受了成功的 HSCT。TREC 缺失的患者经历了更多的 CHH 相关发病率，包括需要输血的贫血、先天性巨结肠和生长不良。没有 TREC 减少的患者需要 HSCT。我们的研究表明，TREC 缺失的 CHH 患者的免疫和临床表型往往比 TREC 减少的患者更严重。在更大的群体中证实这些趋势将有助于指导提供者和家长及时进行 HSCT 转诊，或对患有危及生命疾病的儿童进行具有成本效益的监测。
