Childhood interstitial lung disease due to compound heterozygous
mutations of the ABCA3 gene
Abstract
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.