关键词: 儿童, DNA突变分析, 纤毛运动障碍, 疾病特征

Abstract:

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.

Key words: Child, DNA mutational analysis, Ciliary motility disorders, Disease attributes