[Pulmonary surfactant protein adenosine triphosphate-binding-cassette-A3 gene composite mutations in infant congenital interstitial lung disease: report of a case and review of literature].

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.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.