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.

中文翻译：

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阿米什人队列与软骨毛发发育不良的严重合并免疫缺陷的新生儿筛查随访。

摘要

软骨-头发发育不全（CHH）是一种常染色体隐性隐性，短肢骨骼发育异常，具有可变的免疫表型。免疫功能范围从临床正常到严重的联合免疫缺陷（SCID）。多项研究表明，异常的免疫参数可能无法预测严重的后果。现在，使用T细胞受体切除环（TREC）分析进行新生儿筛查（NBS）可以有效地识别患有SCID风险的严重T细胞缺乏症的婴儿。NBS可以经济有效地鉴定SCID患者，并通过造血干细胞移植（HSCT）改善结局。俄亥俄州报告了两个异常的TREC结果：减少和不存在TREC。这项研究评估了NBS上8例Amish TREC结果异常的Amish CHH患者的实验室和临床差异。有4例TREC缺失的患者和4例TREC降低的患者。缺席的TREC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例TREC缺失的患者被诊断为SCID，其中2例成功进行了HSCT。缺乏TREC的患者经历了更多与CHH相关的发病，包括需要输血的贫血，Hirschsprung病和failure壮成长。没有TREC降低的患者需要HSCT。我们的研究表明，缺少TREC的CHH患者比TREC降低的患者更倾向于出现严重的免疫学和临床表型。在较大的人群中确认这些趋势将指导提供者和父母及时转诊接受HSCT，或对患有威胁生命的疾病的儿童进行具有成本效益的监视监测。