慢性肉芽肿病基因型与感染病原体的相关性  

Correlation between genotype and pathogen in chronic granulomatous disease

作　　者：梁伟玲 李汉广 刘陈菁 钟共 吴倩 刘小权 陈健良 刘宇隆[3] 李珮华 毛华伟[4] 阳晋 Liang Weiling;Li Hanguang;Liu Chenjing;Zhong Gong;Wu Qian;Liu Xiaoquan;Chen Jianliang;Lau Yulung;Lee Pamela;Mao Huawei;Yang Jin(Department of Paediatrics,Hong Kong University-Shenzhen Hospital,Shenzhen 518000,Guangdong Province,China;Department of Rheumatology and Immunology,Shenzhen Children′s Hospital,Shenzhen 518000,Guangdong Province,China;Department of Paediatrics and Adolescent Medicine,Li Ka Shing Faculty of Medicine,the University of Hong Kong,Hong Kong 999077,China;Department of Rheumatology and Immunology,Children′s Hospital of Chongqing Medical University,Chongqing 409912,China;Department of Infectious Disease,Hong Kong University-Shenzhen Hospital,Shenzhen 518000,Guangdong Province,China)

机构地区：[1]香港大学深圳医院儿科,广东深圳518000 [2]深圳儿童医院风湿免疫科,广东深圳518000 [3]香港大学李嘉诚医学院儿童及青少年学系,999077 [4]重庆医科大学附属儿童医院风湿免疫科,409912 [5]香港大学深圳医院感染科,广东深圳518000

出　　处：《中华实用儿科临床杂志》2021年第5期364-368,共5页Chinese Journal of Applied Clinical Pediatrics

摘　　要：目的探讨19例慢性肉芽肿病(CGD)患儿临床特点,了解其发病特点、影像学改变、常见感染病原体及基因突变类型。方法对2012年12月至2018年12月在香港大学深圳医院诊断的19例CGD患儿临床表现、实验室检查、治疗及预后资料进行总结分析。结果通过呼吸爆发检查及基因分析明确诊断19例CGD,均为男童。发病年龄≤1个月13例,诊断年龄为2个月~10岁,母亲为携带者16例。临床主要表现为肺部真菌感染(19/19例)、卡介苗病(14/19例)、淋巴结炎(14/19例)、肛周脓肿(9/19例)、皮肤脓肿(5/19例)和溃疡性结肠炎(2/19例)。微生物培养阳性共59例次,其中真菌9例次,肺炎克雷伯杆菌8例次,分枝杆菌7例次,草绿色链球菌5例次,大肠埃希菌3例次,革兰阳性细菌3例次,金黄色葡萄球菌3例次,洋葱伯克霍尔德菌2例次。19例明确基因诊断,其中CYBB 17例、CYBA 1例、NCF21例。无义突变6例,缺失突变5例(大片段缺失2例),剪接突变3例,错义突变5例。其中5种突变类型目前未见报道。本研究中3例剪接突变患儿皮肤、肛周脓肿及淋巴结炎常见,2例大片缺失突变患儿感染较其他患儿严重。结论在国内,CGD主要表现为肺部感染与播散性卡介苗病。感染谱中,分枝杆菌感染较常见;真菌感染占主要部分,呼吸道是最常感染部位;肛周脓肿以肺炎克雷伯杆菌及大肠埃希菌为主,基因突变类型与临床表型关系有待大数据进一步验证。Objective To summarize the clinical characteristics,common images,pathogens,and gene mutation types of chronic granulomatosis disease(CGD)in 19 children.Methods The clinical manifestations,laboratory findings,treatment,and prognosis of 19 patients diagnosed with CGD in Hong Kong University-Shenzhen Hospital from December 2012 to December 2018 were analyzed.Results The 19 patients were all males and confirmed as CGD by the dihydrorhodamine test and gene sequencing.The age of the first infection was mostly 1 month after birth(13 cases),and the age of clinical diagnosis ranged from 2 months to 10 years.Sixteen mothers were carriers.The patients presented with pulmonary fungal infection(19/19 cases),Bacillus Calmette Guerin(BCG)-osis(14/19 cases),lymphadenitis(14/19 cases),perianal abscess(9/19 cases),skin abscess(5/19 cases)and ulcerative colitis(2/19 cases).There were 59 positive cultures.Pathogens included fungi(9 cases),Klebsiella pneumonia(8 cases),mycobacteria(7 cases),Streptococcus Viridans(5 cases),Escherichia coli(3 cases),gram-positive bacteria(3 cases),Staphylococcus aureus(3 cases),and Burkholderia cenocepacia(2 cases).Gene mutations were found in all 19 patients,including 17 cases of CYBB,1 case of CYBA and 1 case of NCF2.The type of mutations included nonsense mutations(6 cases),deletion mutations(5 cases,including 2 large fragment deletions),splice mutations(3 cases)and missense mutations(5 cases).Five mutations were novel.Splice mutations in 3 cases often led to skin abscess,perianal abscess and lymphadenitis.Two patients with large deletion mutations had more serious infection than other patients.Conclusions In China,CGD is characterized with pulmonary infection and disseminated BCG-osis.Mycobacteria are common pathogens of CGD,and fungi are dominant pathogens of CGD.The most common infection is respiratory infection.Klebsiella pneumonia and Escherichia coli often lead to perianal abscess.The relationship between gene mutation types and clinical phenotypes requires further verification by big data.

关 键 词：慢性肉芽肿 卡介苗病 肺炎克雷伯 剪接突变 大片段缺失 

分 类 号：R725.9[医药卫生—儿科]