Surfactant dysfunction and neurodevelopmental delay: a new ABCA3 mutation

ABCA3 is a transmembrane protein found on the limiting membrane of lamellar bodies of alveolar type II cells. Its role is the transport of phospholipids for surfactant production. Over 200 ABCA3 mutations are known to compromise ABCA3 functions and bring to different phenotypes, from neonatal respiratory distress syndrome to childhood or adult diffuse interstitial lung diseases. We report the case of a19-month-old girl, born at term age, developing respiratory distress six hours after birth. During the first months of life, she developed recurrent long-lasting and oxygen-dependent lower respiratory tract infections, failure to thrive and neurodevelopmental delay. Because a surfactant deficiency was hypothesized, the four genes responsible for primary surfactant dysfunction were analyzed by Next Generation Sequencing. Two mutations were found in the ABCA3 gene (c.2888A > G and c.4714C > T), one inherited from each parent. To our knowledge, there is no previous reporting of correlation between ABCA3 mutation and neurodevelopmental delay. Neurological abnormalities are instead related to another surfactant dysfunction, caused by NKX2-1gene mutation. Fur-ther cases and accurate genetic diagnosis could be useful to validate this new correlation.