干扰素基因刺激蛋白相关婴儿期发病血管病变1例并文献复习

doi:10.3969/j.issn.1673-5501.2019.03.007

摘要/Abstract

摘要： 目的探讨干扰素基因刺激蛋白(STING)相关婴儿期发病血管病变(SAVI)的临床特点、诊断和治疗。方法对1例SAVI患儿的临床表型及基因型进行分析,并通过复习相关文献,分析和总结有关国内外SAVI的文献报道,总结SAVI的临床特征及遗传学特点。结果男,11岁4个月,为反复呼吸道感染、咳嗽、活动耐力下降,查体可见杵状指(趾),实验室检查提示ESR异常升高、ANA及抗心磷脂抗体阳性,肺部高分辨CT提示间质性病变。全外显子测序提示患儿TMEM173基因新生杂合突变:c.463G>A,p.V155M。予托法替尼(每次5 mg,每天2次)治疗有效。文献复习目前国内外已报道SAVI病例31例(包括本文1例),SAVI男性多发,以婴幼儿为主。首发症状以皮疹(58.0%)、呼吸急促(41.9%)及活动受限(48.3%)为主。实验室检查64.5%伴有ESR增快或CRP升高,64.5%出现自身抗体阳性。70.9%患儿肺部影像学提示为间质性肺炎改变。基因检查可明确诊断,SAVI相关的基因突变位于第5号染色体上的TMEM173基因,74.1%为新发突变。Janus激酶抑制剂治疗有效。结论 SAVI为一种罕见的自身炎症性疾病,为TMEM173基因变异,临床上以活动耐力下降、生长受限及间质性肺疾病为主要表现。Janus激酶抑制剂对该病治疗有效。

关键词: STING相关婴儿期发病血管病变, 临床特征, 文献分析

Abstract: Objective To summarize the clinical characteristics of a boy with Stimulator of interferon genes(STING)-associated vasculopathy with onset in infancy(SAVI).Methods The clinical characteristics of a child with SAVI from Qilu Children's Hospital of Shandong University were collected.A literature search (search terms including'STING-associated vasculopathy with onset in infancy'、'STING'、'SAVI'、'autoinflammatory diseases'、and'interferonopathy')was conducted using CNKI、WanFang Data、VIP and EMBASE、PubMed to include recently published SAVI studies (from January 2010 to April 2018).Results A 11-year-old boy, often suffering from recurrent respiratory tract infection(RRTI), presented with coughing, decreased activity endurance and clubbed fingers. His erythrocyte sedimentation rate(ESR) was abnormally elevated. ANA and anticardiolipin antibody were positive, and the High-resolution computed tomography(HRCT) revealed interstitial lung diseases. Genetic mutation of TMEM173(c.463G>A,p.V155M)was confirmed by Sanger sequencing.It was effectively treated with toltinib 5 mg twice a day. At present, 30 cases of SAVI have been reported at home and abroad, including 1 in Chinese and 13 in English. SAVI is more common in males, mainly in infants and young children. The first symptoms were rash (58.0%), shortness of breath (41.9%) and limited activity (48.3%). Laboratory tests were often accompanied by elevated inflammatory markers and positive anti-nuclear antibodies. 70.9% of the pulmonary imaging showed interstitial pneumonia. SLE is easily misdiagnosed in clinic and can be diagnosed by gene examination. JAK inhibitors are effective.Conclusion SAVI is a rare autoinflammatory disease, which is a TMEM173 gene mutation. It is clinically characterized by decreased activity tolerance, growth restriction and interstitial lung disease. Janus kinase inhibitor(JAK) is effective in treating this disease.

Key words: clinical characteristics, Literature analysis, STING-associated vasculopathy with onset in infancy

张岩, 闫秀丽, 孟晨, 宋桂华, 王玲玲. 干扰素基因刺激蛋白相关婴儿期发病血管病变1例并文献复习[J]. 中国循证儿科杂志, 2019, 14(3): 196-200.

ZHANG Yan, YAN Xiu-li, MENG Chen, SONG Gui-hua, WANG Ling-ling. Stimulator of interferon genes-associated vasculopathy with onset in infancy:one case report and literature review[J]. Chinese Journal of Evidence -Based Pediatric, 2019, 14(3): 196-200.

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