A Novel Compound Heterozygous Mutation In ABCA3 Gene In A Child With Interstitial Lung Disease

Object: Mutations in the gene for adenosine triphosphate-binding cassette transporter subfamily A member 3(ABCA3),can cause fatal respiratory distress in term infants,and interstitial lung disease in older children.Limited data are available in the same ABCA3 genotypes with different presentation.We describe a case of siblings whom were found to be compound heterozygotes for ABCA3 gene mutations with different course of lung disease.Method: We reviewed the medical records of a large kindred included four members,for clinical features,radiographic findings,treatment and outcomes.Also analyzed literature about ch ILD in the same kindred associated with ABCA3 gene mutation.Result: The proband is a 11 years and 7 months old girl.The girl consults shortness of breath and cyanosis after exercise for 9 years.Pulmonary function test revealed a restrictive syndrome with a marked reduction in DLCO.High resolution computed tomography(HRCT)scan demonstrated diffuse groundglass opacities and honeycombing shadows,and echocardiography indicated sever pulmonary hypertension(PH).Genetic analysis sequencing of ABCA3 revealed two novel heterozygous variants: c.3241C> T(p.R1081W)and c.3129C>A(p.N1043K).The patient’s clinical symptoms,physiologic and radiographic improved over the 1 year of the treatment with glucocorticoids,hydroxychloroquine and azithromycin.The girl’s brother,16 years old,who carries the same genotype,has no manifestations of ILD and was found diffuse ground glass opacities in the lung CT.Parental studies identified the father as a carrier of mutation c.3241C> T,and the mother as a carrier of the c.3129C> A mutation,both of them had no similar clinical manifestations,and there were only emphysema changes in the chest HRCT.Reviewing the related article had showed that there were 5 studies about ch ILD kindred caused by ABCA3 gene mutation.Patients with the same ABCA3 gene mutation may have different outcomes.Conclusion: 1.The novel compound heterozygous mutation c.3241C>T and c.3129C>A in of ABCA3 gene lead to ch ILD.Treatment with glucocorticoid,hydroxychloroquine and azithromycin was effective to improve patient’s symptoms as well as resolution of ground glass opacities in CT;2.Siblings or relatives with the same ABCA3 variants,but clinical outcomes vary from each other.