| Disorders of surfactant production or metabolism (congenital PAP) |
| Deficiencies in surfactant proteins B and C (SP-B and SP-C, which are encoded by the SFTPB and SFTPC genes, respectively). |
| Variants of ATP-binding cassette, subfamily A (ABCA3). |
| Variants of NK2 homeobox-1 (NKX2.1). This gene encodes thyroid transcription factor-1, which in turn regulates transcription of SFTPC and ABCA3. |
| Variants of SLC7A7/y+LAT1, which causes LPI. Patients with LPI have defective cationic amino acid transport (y+L transport) and defective expression of y+LAT in alveolar macrophages. |
| Variants of methionyl-tRNA synthetase (MARS): Compound heterozygosity is associated with liver failure, PAP, anemia, delays in motor development; exact mechanism of PAP uncertain. |
| Disruption of GM-CSF signaling (primary PAP) |
| Autoimmune PAP: Anti-GM-CSF antibodies. |
| Hereditary PAP: Recessive variants of the genes for GM-CSF receptor, alpha and beta subunits (CSF2RA and CSF2RB). |
| Underlying disorder secondarily affects alveolar macrophages (secondary PAP) |
| Hematologic malignancy (eg, myelodysplastic syndrome, multiple myeloma, chronic myelocytic leukemia, Waldenström macroglobulinemia). |
| Myelodysplastic syndromes (eg, GATA2 gene variants). |
| Hematopoietic cell transplantation for myeloid malignancy. |
| Immune defects (eg, Fanconi syndrome, agammaglobulinemia, severe combined immunodeficiency (especially adenosine deaminase deficiency), Behçet disease, juvenile dermatomyositis, renal tubular acidosis, GATA2 gene variants). |
| Infections (eg, Nocardia, Pneumocystis jirovecii, cytomegalovirus). |
Inhalational exposures: - Inorganic dust inhalation (silica, aluminum, titanium, tin-oxide)
- Organic dust inhalation (agricultural, bakery flour, fertilizer, sawdust)
- Fume inhalation (chlorine, gasoline/petroleum, nitrogen dioxide, paint/varnish, plastic)
|
| Unclassified |
