DNAAF3突变引发原发性纤毛运动障碍一例并文献复习

Primary ciliary dyskinesia for DNAAF3 gene mutations:a case report and literature review

目的:总结因DNAAF3突变引发原发性纤毛运动障碍(primary ciliary dyskinesia,PCD)患儿临床表现、诊治要点及治疗转归。方法:回顾性分析广州医科大学附属第一医院儿科2022年7月9日收治的1例男性PCD患儿(4个月10天)的临床资料及诊治经过,并以“原发纤毛运动障碍DNAAF3基因”检索万方、中国知网、中国生物医学文献数据库,以“primary ciliary dyskinesia DNAAF3”检索PubMed数据库进行文献复习,检索时间截止至2022年8月。结果:患儿出生后(2022年3月1日)因反复“新生儿肺炎/重症肺炎、内脏反位、病理性黄疸、新生儿贫血、新生儿败血症”予以化痰、平喘、抗感染、无创呼吸机辅助通气治疗,疗效不佳。于2022年7月因“反复咳嗽4个月余,加重伴喘息2 d”就诊于广州医科大学附属第一医院。经完善血常规、炎症指标、呼吸道病原学检测、胸部CT扫描、心脏及肝胆脾胰彩色多普勒超声检查后,提示肺部感染(肺炎链球菌、呼吸道合胞病毒、2型副流感病毒感染)、多部位内脏转位;纤维支气管镜检查见左、右支气管镜像倒置;纤毛活检电镜检出纤毛外动力臂缺失明显;全外显子组测序检测证实患儿存在DNAAF3基因突变(c.748_752dupGACGC和c.326G>C),诊断为PCD。予化痰、抗感染、纤维支气管镜灌洗治疗10 d后好转出院。结合检索到的4例由DNAAF3基因突变导致的PCD患者,发现4例患儿确诊年龄均<1岁,另1例也仅10岁。5例患儿均为足月顺产,除本例患儿外,其余均有新生儿呼吸窘迫和鼻窦炎表现。胸部CT扫描提示5例均有内脏左右异位。呼吸道纤毛电镜示1例动力臂稀少、3例内外动力臂缺失、1例外动力臂缺失。5例基因突变染色体位置不同,可见于2、3、4、5、6、12、19号染色体。诊断明确后予抗感染或对症治疗后均转归良好。结论:DNAAF3基因突变可导致儿童原发性纤毛运动障碍,临床表型与基因型相关。临床工作中,对儿童出现内脏转位且反复出现咳嗽、咳痰和鼻窦炎者应提高警惕,可借助鼻呼气一氧化氮检测、呼吸道纤毛电镜检查和基因检测来提高PCD确诊率。

Objective:To review the clinical characteristics,diagnosis,treatment and prognosis of a child with primary ciliary dyskinesia(PCD)caused by DNAAF3 mutations.Methods:Clinical data and treatment process of a 4 months and 10 days old boy with PCD in the Department of Pediatrics,the First Affiliated Hospital of Guangzhou Medical University,were retrospectively reviewed.Wanfang,China National Knowledge Infrastructure,China Biology Medicine Disc and PubMed were searched up to August 2022 using“primary ciliary dyskinesia DNAAF3”as the search terms.Results:After birth(March 1,2022),the child received phlegm reduction,asthma relief,anti-infection and non-invasive ventilator-assisted ventilation due to neonatal pneumonia/severe pneumonia,visceral inversion,pathologic jaundice,neonatal anemia and neonatal sepsis,but the treatment was not effective.In July 2022,he was admitted to our hospital due to“recurrent cough for more than 4 months,aggravated with wheezing for 2 days”.After completion of blood routine examination,inflammatory marker testing,respiratory etiology testing,chest CT scan,color Doppler ultrasound of the heart,liver,bile,pancreas and spleen,he was diagnosed as pulmonary infections(caused by Streptococcus pneumoniae,respiratory syncytial virus,parainfluenza type 2 virus)and multi-site visceral translocation.The fiberoptic bronchoscopy showed that the left and right bronchial images were inverted,and the electromicroscopy of ciliary biopsy showed obvious absence of external ciliary motor arm.In addition,the whole exome sequencing found the presence of DNAAF3 gene mutation(c.748_752dupGACGC and c.326G>C),and the diagnosis was PCD.After 10 days of treatment with phlegm reduction,anti-infection and fiberoptic bronchoscopy,the child was recovered and discharged.We combined our findings with the previous reported characteristics of 4 children with PCD caused by DNAAF3 gene mutation,and found that 4 patients were less than 1 year old and the other was only 10 years old.All the 5 children had full-term natural delivery.Except for the child in our study,all of them had neonatal respiratory distress and sinusitis.Chest CT scan showed that all 5 cases had visceral inversion.Electron microscopy of respiratory cilia showed that 1 case was deficient in motor arm,3 cases were deficient in inner dynein arm and outer dynein arm,and 1 case was deficient in outer dynein arm.However,these 5 cases had different chromosome locations of gene mutations,which can be seen in chromosome 2,3,4,5,6,12,19.The prognosis was good after anti-infection or symptomatic treatment.Conclusion:DNAAF3 mutation can lead to PCD in children,and the clinical phenotype is related to genotype.Clinicians should pay more attention to children with visceral transposition accompanied by recurrent cough,sputum and sinusitis.Nasal and expiratory nitric oxide detection,electron microscopic examination of respiratory cilia and gene detection can improve the diagnosis rate of PCD.