PULMONARY ALVEOLAR PROTEINOSIS, CONGENITAL, 1
INTERSTITIAL LUNG DISEASE, NONSPECIFIC, DUE TO SURFACTANT PROTEIN B DEFICIENCY
INTERSTITIAL LUNG DISEASE DUE TO SURFACTANT PROTEIN B DEFICIENCY
SMDP1
Inborn errors of pulmonary surfactant metabolism are genetically heterogeneous disorders resulting in severe respiratory insufficiency or failure in full-term neonates or infants. These disorders are associated with various pathologic entities, including pulmonary alveolar proteinosis (PAP), desquamative interstitial pneumonitis ... Inborn errors of pulmonary surfactant metabolism are genetically heterogeneous disorders resulting in severe respiratory insufficiency or failure in full-term neonates or infants. These disorders are associated with various pathologic entities, including pulmonary alveolar proteinosis (PAP), desquamative interstitial pneumonitis (DIP), or cellular nonspecific interstitial pneumonitis (NSIP) (Clark and Clark, 2005). The hereditary, often congenital, pulmonary surfactant metabolism dysfunction disorders are distinct from respiratory distress syndrome (RDS; 267450), which affects preterm infants and is associated with the pathologic finding of hyaline membrane disease. Acquired PAP (610910) is an autoimmune disorder characterized by the presence of autoantobodies to CSF2 (138960). - Genetic Heterogeneity of Pulmonary Surfactant Metabolism Dysfunction See also SMDP2 (610913), caused by mutation in the SPTPC gene (178620) on 8p21; SMDP3 (610921), caused by mutation in the ABCA3 gene (601615) on 16p13; SMDP4 (300770), caused by mutation in the CSF2RA gene (306250) on Xp; and SMDP5 (614370), caused by mutation in the CSF2RB gene (138981) on 22q12.
Moulton et al. (1992) reported 2 pairs of sibs from 2 unrelated families with neonatal respiratory distress associated with pulmonary alveolar proteinosis beginning within hours of birth. All were full-term infants and 3 had mature lung profiles. Radiographic ... Moulton et al. (1992) reported 2 pairs of sibs from 2 unrelated families with neonatal respiratory distress associated with pulmonary alveolar proteinosis beginning within hours of birth. All were full-term infants and 3 had mature lung profiles. Radiographic studies showed an early granular pattern followed by lung opacification. All died within 16 to 190 days. Moulton et al. (1992) postulated an inborn error in surfactant processing. Nogee et al. (1993) reported a full-term male infant with surfactant metabolism dysfunction and neonatal respiratory failure who died at 5 months despite intensive supportive treatment with mechanical ventilation and corticosteroids. Open-lung biopsy at age 3 months showed pulmonary alveolar proteinosis with alveoli filled with eosinophilic, granular, PAS-positive material. There were also foamy alveolar macrophages, desquamated alveolar epithelial cells, and extensive interstitial fibrosis with hyperplasia of type II alveolar epithelial cells. Nineteen years earlier, a sister born at term died of respiratory failure at age 1 month. Autopsy revealed alveolar proteinosis and changes consistent with bronchopulmonary dysplasia. Immunoblotting showed absence of the surfactant B protein and mRNA in the proband's lungs and increased amounts of surfactant proteins C and A in alveolar epithelial cells. In an addendum, Nogee et al. (1993) noted that a third affected sib had been born into the family. There was no detectable protein B in the amniotic and lung-lavage fluid, but markedly increased amounts of surfactant protein C were present. The parents were unrelated. Wallot et al. (1999) reported 5 full-term infants, born of a consanguineous kindred of Kurdish descent, who had fatal neonatal respiratory failure shortly after birth. All had pulmonary hypertension and all died despite intensive care. Lung tissue biopsy of 2 infants showed pulmonary alveolar proteinosis. Alveolar walls were thickened with interstitial fibrosis and inflammatory cells and the alveolar spaces were filled with foamy or granular protein-rich exudate and many desquamated cells. Immunostaining of lung tissue demonstrated significantly decreased surfactant SPB and increased SPA (178630) and SPC. One infant also had misalignment of lung vessels, which may have caused pulmonary hypertension. Wallot et al. (1999) noted that the concurrence of misalignment of lung vessels and congenital alveolar proteinosis due to SPB deficiency had not been described before. Tredano et al. (1999) reported a full-term female infant with severe respiratory failure developing hours after birth. She had deep cyanosis, progressive tachydyspnea, hypoxemia, and diffuse, symmetric lung opacifications on chest x-ray. She was managed by mechanical ventilation, but died at age 27 days. Bronchoalveolar lavage fluid showed complete absence of SPB. However, unlike other patients, pro-SPC was processed to the active peptide. Yusen et al. (1999) found that heterozygous relatives of surfactant protein B-deficient infants did not have clinically apparent lung disease. Chetcuti and Ball (1995) reviewed surfactant protein B deficiency. Dunbar et al. (2000) reported 2 unrelated patients of French Canadian descent with a milder form of pulmonary surfactant metabolism dysfunction. The phenotype of both patients was less severe than that reported in other patients with SPB deficiency. The first child underwent bilateral lung transplant at age 4 months and the second child survived to age 6 years with persistent oxygen requirement. The older child developed pulmonary hypertension and right ventricular hypertrophy. Lung tissue biopsy of both patients showed variable alveolar septal widening with increased cellularity and type II pneumocyte hyperplasia. Alveolar spaces were filled with granular eosinophilic material admixed with foamy macrophages and desquamated pneumocytes. Type II pneumocytes contained numerous abnormal lamellar bodies. Advanced staining techniques identified residual SPB in tissue from both patients, although higher levels were observed for the older patient. Both patients had a homozygous mutation in the SFTPB gene (178640.0005) that resulted in a splice site mutation and residual protein activity. The findings indicated that there may be variability in phenotypic expression of surfactant B deficiency and that those with some residual protein activity may survive past the first months of life.
In 3 affected sibs with fatal neonatal respiratory failure and surfactant protein B deficiency, Nogee et al. (1994) identified a homozygous mutation in the SFTPB gene (121ins2; 178640.0001). Both unaffected parents and 2 of 3 healthy sibs were ... In 3 affected sibs with fatal neonatal respiratory failure and surfactant protein B deficiency, Nogee et al. (1994) identified a homozygous mutation in the SFTPB gene (121ins2; 178640.0001). Both unaffected parents and 2 of 3 healthy sibs were heterozygous for the mutation. The same mutation was found in 2 unrelated infants who died from alveolar proteinosis; 1 of these patients was reported by Moulton et al. (1992). DeMello et al. (1994) identified the 121ins2 mutation in 4 of 7 infants from 6 families with congenital surfactant B deficiency associated with pulmonary alveolar proteinosis. In an infant with fatal neonatal respiratory distress and pulmonary alveolar proteinosis due to surfactant B deficiency, Wallot et al. (1999) identified a homozygous mutations in the SFTPB gene (178640.0002). The patient was born to consanguineous Kurdish parents and had 4 similarly affected relatives. In a full-term infant with severe neonatal respiratory distress, Tredano et al. (1999) identified compound heterozygosity for 2 mutations in the SFTPB gene (178640.0001; 178640.0003).
In a review of the disorder, Whitsett and Weaver (2002) stated that approximately 10% of full-term infants who presented with unexplained respiratory failure had mutations in the SFTPB gene.
The incidence of surfactant B deficiency has ... In a review of the disorder, Whitsett and Weaver (2002) stated that approximately 10% of full-term infants who presented with unexplained respiratory failure had mutations in the SFTPB gene. The incidence of surfactant B deficiency has been estimated at 1 in 1.5 million births (Clark and Clark, 2005).