Absence of lamellar bodies with accumulation of dense bodies characterizesa novel form of congenital surfactant defect

Two female sibling full-term newborns developed respiratory distress shortl y after birth, which progressed to respiratory failure. Tracheal lavage dem onstrated presence of surfactant protein A (SP-A), but little surfactant pr otein B (SP-B), without aberrant surfactant protein C (SP-C). On a lung bio psy performed in both infants, prominent type II pneumocyte hyperplasia was evident. Through ultrastructural examination an absence of normally formed lamellar bodies was determined, with numerous irregular electron dense bod ies within the type II pneumocytes. These electron dense bodies could also be identified in the alveolar spaces and alveolar macrophages. No alveolar tubular myelin was present. Abnormally high immunoreactivity for surfactant proteins SP-A, proSP-B, SP-B, and proSP-C was demonstrated by light micros copy. Presence of incompletely processed immunopositive proSP-B, but not pr oSP-C was observed in the alveolar lumina. No mutations in either the SP-B or SP-C gene were identified by sequence analysis of amplified cDNA. We con clude that these siblings exhibit an inherited surfactant deficiency charac terized by abnormal accumulations of surfactant proteins within the pneumoc ytes. This abnormal accumulation may be due to a primary secretory defect, a defect in surfactant phospholipids, or an abnormal interaction between th e phospholipids and surfactant proteins.