Purpose

Combined immunodeficiency (CID), due to mutations in TFRC gene that encodes the transferrin receptors (TfR1), is a rare monogenic disorder. In this study, we further characterize the clinical and immunological phenotypes in a cohort of eight patients.

Methods

A retrospective review of clinical and immunological features of patients diagnosed with a TFRC gene mutation between 2015 and 2019 in three tertiary centers.

Results

Eight patients from six unrelated families were enrolled. The patients had a median age of 7 years (4–32 years). All patients presented with recurrent sinopulmonary infections, chronic diarrhea, and failure to thrive in early life. Less common features were skin abscesses, conjunctivitis, global developmental delay, optic nerve atrophy, vitiligo, multinodular goiter, and hemophagocytic lymphohistiocytosis-like symptoms. All patients had intermittent neutropenia and 87% of the patients had recurrent thrombocytopenia. Anemia was found in 62%. All patients had hypogammaglobinemia and one had a persistent high IgM level. All patients had impaired function of T cells. The same homozygous missense mutation c.58T>C:p.Y20H, in the TFRC gene, was detected in all patients. Stem cell transplantation from matched donors was successful in two patients. Five patients did not receive stem cell transplantation, and they are on prophylactic treatment. One patient died due to severe sepsis and neurological complications.

Conclusion

This report provides a large cohort with a long follow up of patients with this disease. Our cohort showed variable disease severity.

中文翻译：

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8 名患者因 TFRC 突变导致的联合免疫缺陷的临床和免疫学特征。

目的

由于编码转铁蛋白受体 (TfR1) 的TFRC基因发生突变，联合免疫缺陷 (CID)是一种罕见的单基因疾病。在这项研究中，我们进一步表征了一组八名患者的临床和免疫表型。

方法

2015 年至 2019 年在三个三级中心诊断为TFRC基因突变的患者的临床和免疫学特征的回顾性研究。

结果

招募了来自六个无关家庭的八名患者。患者的中位年龄为 7 岁（4-32 岁）。所有患者均出现反复窦肺感染、慢性腹泻和早年发育不良。不太常见的特征是皮肤脓肿、结膜炎、全面发育迟缓、视神经萎缩、白斑、多结节性甲状腺肿和噬血细胞淋巴组织细胞增生症样症状。所有患者都有间歇性中性粒细胞减少症，87% 的患者有复发性血小板减少症。62% 的人发现贫血。所有患者均患有低丙种球蛋白血症，其中一名患者 IgM 水平持续升高。所有患者的 T 细胞功能均受损。TFRC 中相同的纯合错义突变 c.58T>C:p.Y20H基因，在所有患者中检测到。来自匹配供体的干细胞移植在两名患者身上取得了成功。五名患者没有接受干细胞移植，他们正在接受预防性治疗。一名患者死于严重的败血症和神经系统并发症。

结论

该报告提供了一个对患有这种疾病的患者进行长期随访的大型队列。我们的队列显示出不同的疾病严重程度。