When WAS Gene Diagnosis Is Needed: Seeking Clues Through Comparison Between Patients With Wiskott-Aldrich Syndrome and Idiopathic Thrombocytopenic Purpura
When WAS Gene Diagnosis Is Needed: Seeking Clues Through Comparison Between Patients With Wiskott-Aldrich Syndrome and Idiopathic Thrombocytopenic Purpura
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当需要WAS基因诊断时：通过Wiskott-Aldrich综合征和特发性血小板减少性紫癜患者的比较寻找线索
DOI：
10.3389/fimmu.2019.01549
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发表时间：
2019-07-09
影响因子：
7.3
通讯作者：
Chen, Ji
中科院分区：
文献类型：
--
作者：
Jin, Ying-Ying;Wu, Jing;Chen, Ji
工作背景：Wiskott-Aldrich综合征（WAS）是一种罕见的严重X连锁疾病，具有与WAS基因突变类型相关的可变临床表型。在遗传学诊断之前，该综合征很难与特发性血小板减少性紫癜（ITP）鉴别。我们回顾性分析了2004年至2016年转诊至我院的疑似WAS患者，并比较了经基因确诊的WAS患者和经基因诊断的ITP患者的临床特征和实验室检查，以寻求在基因诊断之前区分WAS和ITP的线索。方法：收集78个无血缘关系的家庭中78名疑似WAS患儿。本文回顾性分析了10例儿童的临床资料和实验室检查结果。用流式细胞仪检测外周血淋巴细胞亚群的分布。通过PCR扩增的基因组DNA的直接测序鉴定WASP突变。结果：42例患者最终被诊断为WAS。这些患者的中位发病年龄为1个月（范围：1天-10个月）。中位诊断滞后期为4.6个月（范围：0个月-9.42年）。15例（35.71%）有阳性家族史。超过一半的患者（n = 23，54.76%）有腹泻。肺炎23例（54.76%），重症7例。大出血事件包括皮肤斑点或瘀点（n = 27，64.29%）、直肠周围出血（n = 21，50.00%）、鼻出血（n = 7，16.67%）和颅内出血（n = 2，4.76%）。29例（69.05%）患者患有湿疹，1例患者患有药物过敏。3例患者有自身免疫性疾病，其中2例为自身免疫性溶血性贫血，1例为自身免疫性溶血性贫血合并伊加肾病。共发现42个WASP突变，包括19个新突变。8例患者接受造血干细胞移植（HSCT），均存活。与30例ITP患者相比，WAS患者EOS计数和IgE水平升高，NK细胞计数升高，但CD 8 +T淋巴细胞减少。结论：WAS基因诊断应考虑所有男性ITP样特征，特别是对于非常早的发病年龄，MPV降低（<6.5 fl），EOS计数和IgE水平升高，NK细胞数量增加，CD 8 +T淋巴细胞计数减少的患者。
Background: Wiskott-Aldrich syndrome (WAS) is a rare and severe X-linked disorder with variable clinical phenotypes correlating with the type of mutations in the WAS gene. The syndrome is difficult to differentiate from idiopathic thrombocytopenic purpura (ITP) before genetic diagnosis. We retrospectively reviewed patients suspected to have WAS who were referred to our hospital from 2004 to 2016 and compared the clinical features and laboratory examination of genetically confirmed WAS patients and of patients diagnosed with ITP in order to seek some clues to distinguish WAS and ITP before genetic diagnosis. Methods: Seventy-eight children suspected to have WAS from 78 unrelated families were enrolled in this study. The clinical data and laboratory examination of children were reviewed in the present study. The distribution of lymphocyte subsets from peripheral blood was examined by how cytometry. WASP mutations were identified by direct sequencing of PCR-amplified genomic DNA. Results: Forty-two patients were finally diagnosed with WAS genetically. The median onset age of these patients was 1 month (range: 1 day−10 months). The median diagnosis lag was 4.6 months (range: 0 months−9.42 years). Fifteen patients (35.71%) had positive family histories. More than half of the patients (n = 23, 54.76%) had diarrhea. Twenty-three (54.76%) had pneumonia, 7 with severe symptoms. Major bleeding events included skin spots or petechiae (n = 27, 64.29%), per-rectal bleeding (n = 21, 50.00%), epistaxis (n = 7, 16.67%) and intracranial bleeding (n = 2, 4.76%). Twenty-nine patients (69.05%) had eczema, and one patient had a drug allergy. Three patients had autoimmune diseases, among whom 2 had autoimmune hemolytic anemia and one had autoimmune hemolytic anemia and IgA nephropathy. A total of 42 mutations in WASP were identified, including 19 novel mutations. Eight patients received hematopoietic stem cell transplantation (HSCT) and all survived. Compared with the 30 patients diagnosed with ITP, the WAS patients had higher EOS counts and elevated IgE level, increased NK cell numbers but fewer CD8+T lymphocytes. Conclusion: The WAS gene diagnosis should be considered in all males with ITP-like features, especially for patients with a very early onset age, decreased MPV (<6.5 fl), higher EOS counts and elevated IgE level, increased NK cell number, diminished CD8+T lymphocyte count.