Kok Joo Chan

and 5 more

Introduction: Mutations in adenosine triphosphate-binding cassette transporter A3 (ABCA3) (OMIM:601615) gene was the commonest genetic cause for severe neonatal respiratory distress syndrome (RDS) and childhood interstitial lung disease (chILD). Most literature review has been from patients of Caucasian heritage. Case Description: We report a case of a term male newborn of South East Asian heritage that developed severe respiratory distress soon after birth, and diagnosis was made on clinical, radiological and genetic basis without lung biopsy. He was found to have compound heterozygous variants for the adenosine triphosphate-binding cassette transporter A3 (ABCA3) gene: a novel c.3364G>A (p.Glu1122Lys) variant and previously reported pathogenic c. 737C>T (p.Pro246Leu). The variant c.3364G>A (rs1233043384) was not previously identified in clinical/disease databases such as ClinVar and The Human Gene Mutation Database. Further analysis and bioinformatics study indicated this variant was likely pathogenic. Parental genetic studies revealed parents had one mutation each. Conclusion: Newborns with unexplained respiratory distress syndrome (RDS) and pulmonary surfactant deficiency should have genetic sequencing study. This will be vital for early diagnosis, disease prognostication, treatment planning such lung transplantation, genetic counseling and provide the molecular basis for prenatal diagnosis and pre-implantation genetic diagnosis. It is important to raise awareness of this condition in the Southeast Asia region. Further larger population-based studies are required to determine the frequency of this mutation in our population. ABCA3 deficiency should be considered in term babies who develop severe respiratory distress syndrome in this region.