Congenital alveolar proteinosis caused by a novel mutation of the surfactant protein B gene and misalignment of lung vessels in consanguineous kindred infants.

Abstract

Congenital alveolar proteinosis and misalignment of lung vessels are rare disorders. We report on five infants of consanguineous kindred. All infants were delivered at term after uneventful pregnancies. Shortly after birth they developed respiratory failure and severe persistent pulmonary hypertension. All died despite intensive care. Lung tissue of two infants was studied. Histological examination revealed combination of alveolar proteinosis and misalignment of lung vessels in one patient, alveolar proteinosis in the other. Immunostaining demonstrated surfactant protein B (SP-B) deficiency in both patients' lungs. In a further sibling, analysis of broncho-alveolar lavage fluid showed decreased surfactant protein. PCR and direct sequence analysis of the SP-B gene revealed three novel mutations. One of them, a single base deletion, shifts the reading frame at amino acid 122 and creates a premature termination of translation in exon 6. No mature SP-B protein is produced. Surfactant protein B deficiency caused by mutations of the respective gene and misalignment of lung vessels can concur. Both diseases may have a pathogenetic factor in common.