Details of Disease

General Information of Disease (ID: DISOHFOR)

• Disease Name: Pulmonary alveolar proteinosis with hypogammaglobulinemia
• Synonyms: pulmonary alveolar proteinosis with hypogammaglobulinemia; PAPHG; immunodeficiency (due to OAS1 gain-of-function variant) with pulmonary alveolar proteinosis and hypogammaglobulinemia
• Definition: 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.
• Disease Hierarchy:
  DISYKSRF: Genetic disease
  DISOHFOR: Pulmonary alveolar proteinosis with hypogammaglobulinemia
• Disease Identifiers:
  MONDO ID: MONDO_0020840
  UMLS CUI: C4747984
  OMIM ID: 618042
  MedGen ID: 1648298

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 1 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
OAS1	OT8ZLOCY	Strong	Autosomal dominant	[1]

References

• [1] Heterozygous Mutations in OAS1 Cause Infantile-Onset Pulmonary Alveolar Proteinosis with Hypogammaglobulinemia. Am J Hum Genet. 2018 Mar 1;102(3):480-486. doi: 10.1016/j.ajhg.2018.01.019. Epub 2018 Feb 15.