PARTIAL DEFICIENCY OF SURFACTANT PROTEIN-B IN AN INFANT WITH CHRONIC LUNG-DISEASE

Objective. To evaluate components of pulmonary surfactant and identify mutations in the surfactant protein B gene (SP-B) of a term infant wi th severe respiratory distress and chronic lung disease. Patient and T esting. Respiratory distress developed in an infant delivered at term, and he required extracorporeal bypass support for 2 weeks. Until his unexpected death at 9.5 months, he was ventilator and oxygen dependent and required continual dexamethasone therapy. Tracheobronchial lavage samples were analyzed for content of surfactant proteins (SPs), and D NA from blood samples were sequenced and analyzed by polymerase chain reaction restriction analysis for the presence of SP-B gene mutations. Surfactant lipid composition and function, the contents of SPs and th eir messenger RNAs (mRNAs), and the immunostaining pattern for SPs wer e determined in postmortem lung tissue. Results. The lavage sample con tained SP-A but not SP-B, and DNA restriction analysis indicated that the patient and his mother were heterozygous for the previously descri bed 121ins2 mutation of SP-B. Postmortem lung tissue contained normal levels of SP-A and its mRNA, a low but detectable level of SP-B, and n ear normal content of SP-B mRNA. SP-C was abundant on staining, and so me 6-kd precursor was present in tissue. A surfactant fraction was def icient in phosphatidylglycerol and was not surface active. On DNA sequ encing, a point mutation was found in exon 7 of the patient's SP-B gen e allele without the 121ins2 mutation, resulting in a cysteine for arg inine substitution, and the father was a carrier for the same mutation . Conclusions. We describe a patient who is a compound heterozygote wi th a new mutation and only a partial deficiency of SF-B. Some forms of inherited SP-B deficiency may have low expression of immunoreactive a nd possibly functional SP-B with milder lung disease and longer surviv al. These infants may benefit from glucocorticoid therapy and may not develop antibodies to SP-B after either lung transplant or gene therap y.