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). A clinically similar disorder characterized by respiratory distress (267450) can affect preterm infants, who show developmental deficiency of surfactant. Acquired PAP (610910) is an autoimmune disorder characterized by the presence of autoantibodies 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 Xp22; and SMDP5 (614370), caused by mutation in the CSF2RB gene (138981) on 22q12.

Congenital alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is characterized histologically by failure of formation and ingrowth of alveolar capillaries that then do not make contact with alveolar epithelium, medial muscular thickening of small pulmonary arterioles with muscularization of the intraacinar arterioles, thickened alveolar walls, and anomalously situated pulmonary veins running alongside pulmonary arterioles and sharing the same adventitial sheath. Less common features include a reduced number of alveoli and a patchy distribution of the histopathologic changes. The disorder is associated with persistent pulmonary hypertension of the neonate and shows varying degrees of lability and severity (Boggs et al., 1994). Affected infants present with respiratory distress resulting from pulmonary hypertension in the early postnatal period, and the disease is uniformly fatal within the newborn period (Vassal et al., 1998). Additional features of ACDMPV include multiple congenital anomalies affecting the cardiovascular, gastrointestinal, genitourinary, and musculoskeletal systems, as well as disruption of the normal right-left asymmetry of intrathoracic or intraabdominal organs (Sen et al., 2004).