ABCA3基因复合杂合突变导致儿童间质性肺疾病2例  

ABCA3 gene complex heterozygous mutation leads to interstitial lung disease in children:Two-case report

作　　者：王珍 钟礼立[1] 王俊普[2] 彭力[1] 易迎晴 WANG Zhen;ZHONG Lili;WANG Junpu;PENG Li;YI Yingqing(Children’s Medical Center,First Affiliated Hospital of Hunan Normal University/Hunan Provincial People’s Hospital,Changsha 410005;Department of Pathology,Xiangya Hospital,Central South University,Changsha 410008,China)

机构地区：[1]湖南师范大学附属第一医院/湖南省人民医院儿童医学中心,长沙410005 [2]中南大学湘雅医院病理科,长沙410008

出　　处：《临床与病理杂志》2023年第7期1469-1476,共8页Journal of Clinical and Pathological Research

基　　金：儿童呼吸病学湖南省重点实验室课题(2019TP1043);湖南省出生缺陷协同防治科技重大专项(2019SK1014)

摘　　要：ABCA3基因突变是一种与遗传相关的疾病,为肺表面活性物质代谢缺陷疾病的一种。后者是引起间质性肺疾病(interstitial lung disease,ILD)的重要原因之一。ILD是一类在临床表现、影像学表现和病理学检查上都有相同特征,但病因各异的疾病。2020年湖南省某医院儿科收治确诊的2例因ABCA3基因复合杂合突变导致儿童ILD的病例,其临床特点为咳嗽、呼吸快、活动不耐受、低氧血症、生长及发育迟缓等,肺部影像学提示间质性病变,病理活检提示脱屑性ILD,电镜下可见异常嗜锇性板层小体,基因诊断提示为ABCA3基因复合杂合突变。因此当患儿的临床表现及影像学结果高度符合ILD时,需要考虑ABCA3基因相关性肺疾病,可以通过完善基因检测明确病因,与此同时肺活检的病理结果(电镜和光镜)也是临床上对该病进行诊断和治疗的重要方式。该病常规治疗效果欠佳,在加用羟氯喹治疗后患儿临床症状有不同程度好转,随访时患儿的临床表现和复查的胸部影像学表现均好转。说明羟氯喹对ABCA3复合杂合突变疾病有一定疗效,为临床医生在该病的治疗方面提供了更多的可能。ABCA3 gene mutation is a genetically related disease,which is one of the metabolic defects of lung surface active substances.The latter is one of the important causes of interstitial lung disease(ILD).ILD is a kind of disease with the same characteristics in clinical manifestations,imaging findings and pathological examination,but different etiology.Two cases of pediatric ILD due to complex heterozygous mutation of ABCA3 gene confirmed by the Children’s Respiratory Department of Hospital in 2020. Their clinical characteristics were cough, rapid breathing, activity intolerance, hypoxemia, and growth retardation. Lung imaging suggested interstitial lesions;pathological biopsy suggested desquamation ILD;electron microscope showed abnormal osmiophilic multilamellar bodies;genetic examination suggested complex heterozygous mutation of ABCA3 gene. Therefore, when the clinical manifestations and imaging findings of a child are highly consistent with ILD, ABCA3 gene related lung disease should be considered. Genetic testing can be improved to identify the cause of the disease for subsequent treatment. At the same time, the pathological results of lung biopsy (electron microscope and light microscope) are also important methods for clinical diagnosis and the treatment of the disease. The conventional treatment of this disease was not effective, and the clinical symptoms of the children improved to varying degrees after the addition of hydroxychloroquine treatment. The clinical manifestations of the children and the results of chest imaging examination after review were significantly improved during follow-up. It is indicated that hydroxychloroquine is effective in the treatment of ABCA3 compound heterozygous mutation in children with the disease, which provides more possibilities for clinicians in the treatment of children with the disease.

关 键 词：儿童间质性肺疾病 ABCA3基因突变 嗜锇性板层小体 羟氯喹 

分 类 号：R725.6[医药卫生—儿科]