Genetic Abnormalities of Surfactant Metabolism

Nogee, Lawrence M.; Wert, Susan E.

Pulmonary surfactant is the complex mixture of lipids and proteins needed to reduce alveolar surface tension at the air-liquid interface and prevent alveolar collapse at the end of expiration. It has been recognized for almost 50 years that a deficiency in surfactant production due to pulmonary immaturity is the principal cause of the respiratory distress syndrome (RDS) observed in prematurely born infants.1 Secondary surfactant deficiency due to injury to the cells involved in its production and functional inactivation of surfactant is also important in the pathophysiology of acute respiratory distress syndrome (ARDS) observed in older children and adults.2,3 In the past 15 years, it has been recognized that surfactant deficiency may result from genetic mechanisms involving mutations in genes encoding critical components of the surfactant system or proteins involved in surfactant metabolism.4,5 Although rare, these single gene disorders provide important insights into normal surfactant metabolism and into the genes in which frequently occurring allelic variants may be important in more common pulmonary diseases.