Fatal familial surfactant protein B deficiency.

Fatal familial surfactant protein B deficiency EDrroR,-In 1993 a sibship of three infants who died of hyaline membrane disease had had an absence of surfactant protein B (SP-B) and its mRNA in lung tissue.' The gene coding for SP-B has been located and a frameshift mutation in this gene has been identified in the reported sibship and in two other families .2 A further six cases of SP-B deficiency with varying clinical and genetic findings have been described.3 We describe the first British cases in two siblings. Case 1 This first girl of healthy, non-consan-guineous, caucasian parents was born in 1991, at termn, weighing 3-5 kg. Apgar scores were nine and 10 at one and five minutes, respectively. At 5 hours of age she developed respiratory distress and was mechanically ventilated. She received maximal ventilation and failed to respond to artificial surfactant, Tolazoline, or prostacyclin. She died at 53 hours of age. The clinical diagnosis at death was persistent fetal circulation. Postmortem examination found extensive hyaline membrane with no evidence of pulmonary artery hyperplasia. Occasional alveoli contained granular eosinophilic material. Case 2 This boy, the index case, was born at term, weighing 3-2 kg after a normal pregnancy, labour, and delivery. Apgar scores were nine and 10 at one and five minutes, respectively. Respiratory distress was evident from 1 hour of age and mechanical ventilation was started at 16 hours. He remained ventilator dependent until death. Chest x ray pictures showed severe hyaline membrane disease and remained unchanged throughout the course of his illness. There was only a transient response to artificial surfactant, Dexametha-sone, and high frequency oscillation. No microbial pathogens were identified and echocardiography was normal. Open lung biopsy on day 21 showed alveoli filled with granular eosinophilic material staining positive with periodic acid Schiff. Degenerating foamy and granular macro-phages were present. Immunohistochemistry showed undetectable concentrations of SP-B in lung tissues. SP-B was undetectable by enzyme linked immunosorbent assay (ELISA) in tracheal aspirates, and accumulation of a pro-SP-C fragment, typical of SP-B deficiency disease, was present (personal communication, J Whitsett, Cincinnati). DNA studies identified the known mutation in one allele (personal communication, L Nogee, Baltimore). Following informed consent from both parents, ventilation was elec-tively discontinued on day 32. Comment These tWO infants illustrate the clinical presentation of this newly diagnosable condition. The histological findings are identical with those seen in pulmonary alveolar proteinosis, a rare alveolar disease described in …