摘要:
Objective To report a case of the pulmonary surfactant protein (SP) adenosine triphosphate-binding-cassette-A3 (ABCA3) gene mutations in infant congenital interstitial lung disease (ILD),and review the related literature,to investigate the relationships of ABCA3 gene mutation associated with ILD in infants.Method A 6-months-old boy was hospitalized in the department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University.The clinical,radiological,histological information from transbronchial lung biopsy (TBLB) and genetic testing in this case was analyzed;12 reports retrieved on literature search at Pubmed,OVID databases from 2004 to 2015 by using the ABCA3 as keyword were reviewed and analyzed.Result (1) The patient,a 6-months-old boy,had progressive tachypnea and dyspnea since 4 months old.Physical examination on admission revealed respiratory rate of 78 times/min,heart rate of 187 times/min,SpO2 0.93 (mask oxygen-inspiration with 6 L/min),scattered fine moist crackles could be heard over the both lungs,clubbing fingers were found.High-resolution computed tomography(HRCT) revealed diffuse ground-glass opacity,interlobular and intralobular septal thickening.Lung biopsies showed evidences of the alveolar cavity atelectatic changes and interstitial fibrosis.SP-A and SP-B were negative in immunohistochemical stainting.SP-related gene sequence analysis found that there was compound heterozygous missense mutation of ABCA3 gene in c.1942A > G,c.2701-33G > C and c.991-105C > A.(2) The review of related literature found that totally 12 cases were reported.The main manifestations were progressive tachypnea and dyspnea,age of onset was between birth and 4 years of age.The imaging characteristics of chest HRCT revealed diffuse infiltration or diffuse ground-glass pattern in the lung.Prognosis:6 cases died,and 6 cases survived,including 4 cases with pulmonary function disturbance to different degrees;12 cases had ABCA3 gene mutations,9 cases had composite ABCA3 gene mutations,in 11 cases the mutation occured in the exon of coding region,in 1 case in the intron,9 cases had heterozygous mutations,3 cases had homozygous mutations.Conclusion The main phenotypes of ABCA3 mutation associated with ILD were full term neonatal respiratory distress syndrome or progressive tachypnea or dyspnea unexplained in infants.The chest HRCT showed two diffuse pulmonary interstitial changes.ABCA3 mutation mainly was multi-site composite mutations and heterozygous mutations in the exon of coding region.%目的 报道1例肺表面活性蛋白ATP结合盒A家族成分3(ABCA3)基因突变相关性婴儿肺间质疾病(ILD),复习文献并探讨ABCA3基因突变与婴幼儿ILD相关性.方法 总结、分析2014年12月广州医科大学附属第一医院儿科收治的1例ILD病例的临床、影像、肺组织病理特点与基因检测结果,并以“ABCA3”为主题词,在PubMed、OVID数据库检索2004至2015年的相关病例报道,进行文献复习.结果 (1)患儿男,6月龄,4月龄起进行性气促,唇周发绀,呼吸困难.入院时情况:呼吸78次/min,心率187次/min,面罩吸氧6 L/min下氧饱和度0.93,三凹征明显,双肺可闻及固定湿性啰音,有杵状指(趾).胸部CT:两肺弥漫磨玻璃密度影,肺间质增厚.经支气管镜肺组织活检病理结果:肺泡腔萎陷,间质轻度纤维化.免疫组织化学:表面活性蛋白(SP)-A、SP-B无表达.肺表面活性蛋白相关基因检测结果:ABCA3 c.1942A>G及c.2701-33G>C、c.991-105C>A复合突变.(2)复习文献:检索到相关文献12篇12例,均为足月儿,发病年龄:生后0h~4岁,均以进行性气促,呼吸困难为主要表现,影像学表现为两肺弥漫网格状改变或磨玻璃样变.预后:6例死亡,6例存活,其中4例有不同程度的肺功能障碍.12例患儿基因检测均有ABCA3基因突变,9例为ABCA3基因复合突变,突变位点11例在编码区外显子处,1例在内含子处,9例为杂合突变,3例为纯合突变.结论 ABCA3基因突变相关性ILD多表现为足月儿的呼吸窘迫综合征或婴儿期不明原因的进行性气促、呼吸困难,影像学呈两肺弥漫间质改变.ABCA3基因突变以多位点复合突变多见,多为编码区外显子处杂合突变.