has material basis in germline mutation in OAS1 hereditary disease respiratory system disorder pulmonary alveolar proteinosis with hypogammaglobulinemia https://github.com/monarch-initiative/mondo/issues/5261 https://github.com/monarch-initiative/mondo/issues/9468 https://www.malacards.org/card/immunodeficiency_100_with_pulmonary_alveolar_proteinosis_and_hypogammaglobulinemia https://www.malacards.org/card/infantile_onset_pulmonary_alveolar_proteinosis_hypogammaglobulinemia A primarily a lung disorder characterized by onset of respiratory insufficiency due to pulmonary alveolar proteinosis (PAP) in the first months of life. Affected individuals may have normal respiratory function at birth. Development of the disorder appears to be influenced or triggered by viral infection, manifest as progressive respiratory insufficiency, confluent consolidations on lung imaging, and diffuse collection of periodic acid-Schiff (PAS)-positive material in pulmonary alveoli associated with small and nonfoamy alveolar macrophages. Patients also have hypogammaglobulinemia, leukocytosis, and splenomegaly. Many patients die of respiratory failure in infancy or early childhood; hematopoietic stem cell transplantation (HSCT) is curative. The pathogenesis may be related to abnormal function of alveolar macrophages, resulting in decreased catabolism of surfactant. The disorder results from a gain-of-function effect that particularly affects B cells and monocytes. MEDGEN:1810375 Orphanet:572428 immunodeficiency (due to OAS1 gain-of-function variant) with pulmonary alveolar proteinosis and hypogammaglobulinemia UMLS:C5680364 pulmonary alveolar proteinosis with hypogammaglobulinemia GARD:0022313 OAS1 deficiency MONDO:0020840 OMIM:618042 UMLS:C4747984 PAPHG DOID:0061070 OAS1-related infantile-onset pulmonary alveolar proteinosis-hypogammaglobulinemia MEDGEN:1648298 infantile-onset pulmonary alveolar proteinosis-hypogammaglobulinemia