Normal lung function in subjects heterozygous for surfactant protein-B deficiency

Inherited deficiency of surfactant protein-B (SP-B) is a fatal autosomal recessive disorder of lung cell metabolism caused most frequently by a frameshift mutation in codon 121 of the SP-B gene (121ins2) and is characterized by rapidly progressive respiratory failure immediately after birth. Lungs from genetically engineered heterozygous SP-B-deficient mice exhibit decreased compliance and mild air trapping. To determine whether pulmonary function of heterozygous SP-B-deficient humans is similarly affected, we studied nine heterozygous subjects 16 to 44 yr of age and two unaffected subjects 7 and 23 yr of age from five families of 121ins2 SP-B-deficient infants. An increase in residual volume was noted in one heterozygous family member and one unaffected family member. Compliance, maximal transpulmonary pressure, air flow, and gas exchange were normal in all heterozygous subjects tested. These data suggest that humans heterozygous for the 121ins2 mutation have normal pulmonary function through the first four decades of life. The impact of advancing age and environmental exposures on the lung function of heterozygotes remains to be determined.