Hereditary surfactant protein B deficiency resulting from a novel mutation.

Hereditary surfactant protein B (SP-B) deficiency is an autosomal recessive disease in which affected infants are unable to produce normally functional surfactant, resulting in neonatal respiratory failure and death within the first year of life. The most common cause of SP-B deficiency is a frameshift mutation in exon 4 (121ins2) of the SP-B gene. We report a newborn infant who had onset of respiratory distress during the first days, was unresponsive to exogenous surfactant, corticosteroids, prostacyclin, high frequency oscillatory ventilation and inhaled nitric oxide, and died after 27 days. Immunostaining of lung tissue obtained at biopsy demonstrated absent staining for SP-B, and robust extracellular staining for proSP-C, findings characteristic for SP-B deficiency. DNA analysis revealed the 121ins2 mutation on one of her SP-B alleles and a novel mutation, 122delC, on her other SP-B allele. The proximity of the novel mutation in exon 4 allele found in this infant to the 121ins2 supports the notion that this region may represent a "hot spot" for SP-B gene mutations and confirms the heterogeneity of mechanisms which lead to SP-B deficiency. Hereditary SP-B deficiency is a rare, newly diagnosable and probably under-recognized disease, which should be suspected in term newborn infants with unexplained respiratory failure.