TY - JOUR
T1 - Surfactant protein B deficiency
T2 - Antenatal diagnosis and prospective treatment with surfactant replacement
AU - Hamvas, Aaron
AU - Cole, F. Sessions
AU - deMello, Daphne E.
AU - Moxley, Michael
AU - Whitsett, Jeffrey A.
AU - Colten, Harvey R.
AU - Nogee, Lawrence M.
N1 - Funding Information:
Congenital pulmonary alveolar proteinosis, an uncommon cause of respiratory failure in newborn term infants, is characterized by ah, eolar accumulation of lipid and protein-rich surfactant material and is uniformly fatal. I-s Supported in part by the American Lung Association of Eastern Missouri (A.H.), the American Lung Association (D.E.d.M.), the National Institutes of Health (NIH HL-34748 \[D.E.d.M.\]N, IH HL-38859 \[J.A.W.\],a nd NIH HL-37591 \[H.R.C.\], and the March of Dimes Basil O'Connor Award (L.M.N.). Submitted for publication March 11, 1994; accepted April 26, 1994. Reprint requests: Aaron Hamvas, MD, St. Louis Children's Hospital, Division of Newborn Medicine, One Children's Place, St. Louis, MO 63110. Copyright 9 1994 by Mosby-Year Book, Inc. 0022-3476/94/$3.00 + 0 9/20/56967
PY - 1994/9
Y1 - 1994/9
N2 - An infant with a family history of congenital alveolar proteinosis associated with surfactant protein B (SP-B) deficiency was identified when SP-B was not detected in amniotic fluid obtained at 37, 38, and 40 weeks of gestation. Surfactant replacement with commercially available preparations that contained SP-B was begun soon after delivery. Progressive respiratory failure developed despite continued surfactant replacement, corticosteroid therapy, and extracorporeal membrane oxygenation. The infant died at 54 days of age while awaiting lung transplantation. Surfactant extracted from amniotic fluid, bronchoalveolar lavage fluid, and lung tissue had no phosphatidylglycerol; surface tension was 24 dynes/cm (normal, <10 dynes/cm) and did not decrease with in vitro addition of exogenous SP-B. Pulmonary vascular permeability measured with positron emission tomography was twice normal. At autopsy the alveolar proteinosis pattern was less prominent than that seen in affected siblings. Immunoreactivity of SP-B was absent in type II cells, but numerous foreign body granulomas with central immunoreactivity for SP-B and surfactant protein C were present. We conclude that exogenous surfactant replacement did not normalize surfactant composition, activity, or pulmonary vascular permeability. These findings suggest that endogenous SP-B synthesis is necessary for mature surfactant metabolism and function.
AB - An infant with a family history of congenital alveolar proteinosis associated with surfactant protein B (SP-B) deficiency was identified when SP-B was not detected in amniotic fluid obtained at 37, 38, and 40 weeks of gestation. Surfactant replacement with commercially available preparations that contained SP-B was begun soon after delivery. Progressive respiratory failure developed despite continued surfactant replacement, corticosteroid therapy, and extracorporeal membrane oxygenation. The infant died at 54 days of age while awaiting lung transplantation. Surfactant extracted from amniotic fluid, bronchoalveolar lavage fluid, and lung tissue had no phosphatidylglycerol; surface tension was 24 dynes/cm (normal, <10 dynes/cm) and did not decrease with in vitro addition of exogenous SP-B. Pulmonary vascular permeability measured with positron emission tomography was twice normal. At autopsy the alveolar proteinosis pattern was less prominent than that seen in affected siblings. Immunoreactivity of SP-B was absent in type II cells, but numerous foreign body granulomas with central immunoreactivity for SP-B and surfactant protein C were present. We conclude that exogenous surfactant replacement did not normalize surfactant composition, activity, or pulmonary vascular permeability. These findings suggest that endogenous SP-B synthesis is necessary for mature surfactant metabolism and function.
UR - http://www.scopus.com/inward/record.url?scp=0028141524&partnerID=8YFLogxK
U2 - 10.1016/S0022-3476(05)83276-7
DO - 10.1016/S0022-3476(05)83276-7
M3 - Article
C2 - 8071741
AN - SCOPUS:0028141524
SN - 0022-3476
VL - 125
SP - 356
EP - 361
JO - The Journal of Pediatrics
JF - The Journal of Pediatrics
IS - 3
ER -