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In this disorder, the alveoli are filled with periodic acid-Schiff (PAS)-positive proteinaceous material that is chemically similar to surfactant. Significant respiratory problems leading to severe hypoxemia, recurrent pulmonary infections, and cardiac problems.

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Alveolar Lipoproteinosis; Alveolar Phospholipidosis; Pulmonary Alveolar Phospholipoproteinosis.

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First described in 1958. Two forms were recognized: (1) primary or idiopathic and (2) secondary to lung infections, hematologic malignancies, inflammation from mineral dusts such as silica, titanium oxide, aluminum, and insecticides.

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Approximately 410 patients have been described. In the United States, the estimated prevalence is established at 1 case per 100,000. Mortality rates can be as high as 30% in the secondary PAP form, depending on the underlying cause is less than 10% in the primary form. There is a male predominance (2.6:1) in adults, but not in children.

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The congenital form seems to be transmitted in an autosomal recessive way and the mutation most commonly responsible is a frameshift mutation in the surfactant protein B (SP-B) gene and maps to 22q12.2-q13.1. The late-onset form is usually idiopathic or associated with lymphoproliferative disorders or infection (HIV, tuberculosis). The male:female ratio is 3:1.

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The cause of the congenital form of pulmonary alveolar proteinosis could be an inborn error of surfactant metabolism. There is evidence that the disease is caused by a mutation in pulmonary surfactant-associated protein-B (SP-B), resulting in deficiency or absence of this protein, which is also involved in the formation of tubular myelin (surfactant is initially stored in lamellar bodies after its synthesis, to then be secreted as tubular myelin, which is required to form the surfactant film in the alveoli). Another theory focuses on a congenital or acquired defect in the β chain of the GM-CSF (granulocyte-macrophage colony-stimulating factor) receptor (this β chain is common to GM-CSF-2-RB [granulocyte-macrophage colony-stimulating factor receptor beta], CSF-2-, interleukin-3-, and interleukin-5-receptors). This results in defective activation of alveolar macrophages by GM-CSF and decreased local recycling of surfactant proteins. The net result is an imbalance in the homeostasis between production of surfactant and its clearance by alveolar macrophages and the mucociliary elevator.

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Confirmed by bronchoalveolar lavage and/or lung biopsy that shows alveoli filled with PAS-positive proteinaceous material. The bronchoalveolar lavage material looks cloudy or milky and the cytologic examination shows foamy macrophages, reactive pulmonary pneumocytes, and cholesterol crystals. The alveolar architecture and intralobular septae are usually well preserved and the conductive airways unaffected. The congenital form is characterized by absent surfactant protein B. The chest radiograph shows bilateral pulmonary infiltrates (ground-glass aspect) with hilar prominence (bat-wing shape) and progression to fibrosis and a “honeycomb” appearance.

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Neonatal-onset form: The neonate presents with acute respiratory distress with marked hypoxemia shortly after birth. Initially, the symptoms are indistinguishable from hyaline membrane disease (neonatal respiratory distress syndrome). Slow resolution of the initial illness, pneumonia, or persistence of atelectases result in prolonged ventilator dependence. All reported infants with congenital alveolar proteinosis died within the ...

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