Wiskott-Aldrich综合征合并克罗恩病一例并文献复习

doi:10.16150/j.1671-2870.2022.03.010

摘要/Abstract

摘要：

目的：分析1例克罗恩病合并Wiskott-Aldrich综合征（Wiskott-Aldrich syndrome, WAS）患儿的临床、结肠镜表现及其基因特征,为临床诊断提供参考。方法：回顾性分析1例克罗恩病合并WAS患儿的临床表现和生化指标、结肠镜检查、基因检测结果以及其治疗、随访情况,并在PubMed、中国知网、万方数据库中检索相关文献,综合分析。结果：患儿为6岁男童,表现为反复腹痛、便血1个月及肛周脓肿半个月,并从婴儿期出现血小板计数减少。实验室检查提示患儿存在中度贫血（血红蛋白70 g/L）,血小板（77×10⁹/L）降低,红细胞沉降率（71 mm/h）升高,粪钙卫蛋白（大于1 800 μg/g）升高;电子结肠镜检查提示结肠多发溃疡,肠镜活检病理提示末端回肠及全结肠黏膜慢性活动性炎,部分伴局灶微脓肿和隐窝脓肿。该患儿被诊断为克罗恩病。基因检测显示其WAS基因外显子8上剪接位点出现半合子突变（c.777+3_777+6del GAGT）,根据美国医学遗传与基因组学学会指南,该突变为可能致病性突变,故确诊为克罗恩病合并WAS。文献复习共检索到9篇炎症性肠病（inflammatory bowel disease, IBD）合并WAS基因突变病例的文献,共16例患者,均为幼年起病（1 d~14.9岁）,其中10例伴有血小板减少。治疗方法包括药物、手术及骨髓移植等,获得随访的7例患者中有3例死亡。结论：对于儿童IBD患者,尤其是极早发型儿童IBD患者,应考虑单基因突变致病的可能性,如男性IBD患儿伴有自幼出现的血小板减少时,应检测WAS基因。

关键词: 极早发型炎症性肠病, 克罗恩病, Wiskott-Aldrich综合征, 原发性免疫缺陷, 血小板减少

Abstract:

Objective: To investigate the clinical features, endoscopic manifestations, and genetic characteristics of a child with Wiskott-Aldrich syndrome(WAS) and Crohn′s disease, so as to provide reference for clinical diagnosis. Methods: The clinical manifestations, biological indicators, endoscopic characters, therapy, and follow-up of a child with Crohn′s disease combined with WAS were analyzed retrospectively. And literature was searched from PubMed, Wanfang Data, and CNKI. Results: A 6-year-old boy had recurrent abdominal pain, hematochezia for one month, and had perianal abscess for about half a month. He also had thrombocytopenia since infancy. Complete blood cell count showed moderate anemia (Hb 70 g/L) and decreased platelets (77×10⁹/L). The boy had elevated erythrocyte sedimentation rate (71 mm/h) and fecal calprotectin (>1 800 μg/g). Colonoscopy showed multiple ulcers in colon and the pathological examination revealed chronic inflammation in mucosa of the terminal ileum and colon, some of which were accompanied by microabscess and crypt abscesses. The child was diagnosed with Crohn's disease. A splicing mutation (c.777+3_777+6 del GAGT) was identified in the exon 8 of WAS gene by next-generation sequencing. Consequently, the child was definitely diagnosed as WAS combined with Crohn′s disease. There were 9 relevant articles, showing that all 16 patients had childhood-onset inflammatory bowel disease (IBD) (1 day to 14.9 years old), and 10 of them were accompanied by thrombocytopenia. Various treatments, including drugs, surgery, and bone marrow transplantation were required. Seven patients were followed up, and three of them died. Conclusions: For children with IBD, particularly those with very early-onset inflammatory bowel disease, the possibility of monogenic diseases should be taken into account. If a male child with IBD have thrombocytopenia since childhood, the WAS gene should be detected.

Key words: Very early-onset inflammatory bowel disease, Crohn's disease, Wiskott-Aldrich syndrome, Primary immunodificiency, Thrombocytopenia

中图分类号:

R574

刘萍, 肖园, 王歆琼, 陆亭伟, 赵雪松, 杨媛艳. Wiskott-Aldrich综合征合并克罗恩病一例并文献复习[J]. 诊断学理论与实践, 2022, 21(03): 349-354.

LIU Ping, XIAO Yuan, WANG Xinqiong, LU Tingwei, ZHAO Xuesong, YANG Yuanyan. Crohn′s disease in a child with Wiskott-Aldrich syndrome: a case report and literature review[J]. Journal of Diagnostics Concepts & Practice, 2022, 21(03): 349-354.

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参考文献 17

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文献出处	发病年龄	肠道表现	WAS相关表现	其他表现	基因突变	治疗	预后
Folwaczny^[7]	幼时	UC	血小板低,反复感染	无	c.95C>T	泼尼松龙、美沙拉嗪, 结肠切除术	死亡
Cannioto^[8]	15 d	CD	血小板低,湿疹	无	-	骨髓移植	缓解
	1 d	IBD-U	血小板低,湿疹	无	-	骨髓移植	死亡（18个月）
	1 d	UC	血小板低	无	-	骨髓移植	死亡（16个月）
Ohya^[9]	12岁	CD	湿疹	无	c.1378C>T,p.P460S	美沙拉嗪、硫唑嘌呤、英夫利昔单抗	缓解
	11岁	UC	无	无	c.1378C>T,p.P460S	美沙拉嗪、硫唑嘌呤	缓解
	2岁	UC	无	无	c.1378C>T,p.P460S	美沙拉嗪、泼尼松龙灌肠	缓解
Ashton^[10]	11.5岁	UC	间歇性血小板减少、反复感染	原发性硬化性胆管炎	c.1378C>T,p.P460S	硫唑嘌呤、英夫利昔单抗、阿达木、全结肠切除	-
	14.9岁	UC	无	原发性硬化性胆管炎	c.1378C>T,p.P460S	硫唑嘌呤、全结肠切除	-
	14.3岁	CD	无	肛周脓肿、肛瘘	c.391G>A,p.E131K	硫唑嘌呤,肛周手术	-
	13.5岁	CD	无	无	c.391G>A,p.E131K	硫唑嘌呤、英夫利昔单抗	-
Esmaeilzadeh^[11]	8个月	UC	血小板低,反复感染	无	c.360+1G>C	-	-
Zhang^[12]	20 d	IBD	血小板低、湿疹	无	431G>A	-	-
	23 d	IBD	血小板低、湿疹	无	IVS8+1 to +6delGAGT	-	-
	2个月	IBD	血小板低、湿疹	无	923-924 dupGC	-	-
	3个月	IBD	血小板低、湿疹	无	IVS8+1 G>A	-	-