{"orpha":264675,"name":"Hereditary pulmonary alveolar proteinosis","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["Congenital PAP","Congenital pulmonary alveolar proteinosis"],"definition":"A rare, genetic, interstitial lung disease due to mutations in the CSF2R (colony-stimulating factor 2 receptor) alpha or beta subunits and characterized by alveolar accumulation of pulmonary surfactant, presenting a highly variable clinical presentation, ranging from asymptomatic to severe respiratory failure. Characteristic lung biopsy findings include periodic acid-Schiff-positive, granular eosinophilic material, enlarged foamy alveolar macrophages, and well-preserved alveolar walls. The Granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor function is impaired but GM-CSF receptor autoantibodies are absent.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-264675/","orphanet_url":"https://www.orpha.net/en/disease/detail/264675","names":{"fr":{"name":"Protéinose alvéolaire pulmonaire héréditaire","synonyms":["Protéinose alvéolaire pulmonaire congénitale","PAP congénitale"],"definition":"Maladie pulmonaire rare, génétique et interstitielle, due à des mutations des sous-unités alpha ou bêta du CSF2R (récepteur du facteur 2 stimulant les colonies) et caractérisée par une accumulation de surfactant dans les alvéoles pulmonaires, présentant un tableau clinique très variable, allant d'asymptomatique à l'insuffisance respiratoire sévère. Les signes caractéristiques des biopsies pulmonaires sont des dépôts éosinophiles granuleux prenant fortement la coloration PAS (Periodic Acid of Schiff), des macrophages alvéolaires agrandis, d'aspect spumeux, et des parois alvéolaires bien préservées. La fonction des récepteurs du facteur de stimulation des colonies de granulocytes-macrophages (GM-CSF) est altérée, en l'absence d'auto-anticorps des récepteurs du GM-CSF."},"de":{"name":"Pulmonale Alveolarproteinose, hereditäre Form","synonyms":["Alveolarproteinose, pulmonale kongenitale","PAP, kongenitale"],"definition":"Eine genetisch bedingte interstitielle Lungenerkrankung, die auf Mutationen in den Alpha- oder Beta-Untereinheiten des CSF2R (Colony-stimulating factor 2 receptor) zurückzuführen ist und durch eine alveoläre Anhäufung von pulmonalem Surfactant gekennzeichnet ist, mit einem sehr variablen klinischen Bild, das von asymptomatisch bis zu schwerem Atemversagen reicht. Zu den charakteristischen Lungenbiopsiebefunden gehören PAS-Reaktion-positives, granuläres eosinophiles Material, vergrößerte, schaumige Alveolarmakrophagen und gut erhaltene Alveolarwände. Die Funktion des Rezeptors für den Granulozyten-Makrophagen-Kolonie-stimulierenden Faktor (GM-CSF) ist beeinträchtigt, aber es gibt keine GM-CSF-Rezeptor-Autoantikörper."},"es":{"name":"Proteinosis alveolar pulmonar hereditaria","synonyms":["PAP congénita","Proteinosis alveolar pulmonar congénita"],"definition":"Es una enfermedad pulmonar intersticial, genética y poco frecuente, debida a mutaciones en las subunidades alfa o beta del CSF2R (receptor del factor estimulante de colonias tipo 2) y caracterizada por el acúmulo de surfactante pulmonar en los alveolos y por una presentación clínica muy variable, que va desde asintomática a insuficiencia respiratoria grave. Los hallazgos característicos de la biopsia pulmonar incluyen material granular eosinofílico positivo para ácido peryódico de Schiff, macrófagos alveolares espumosos agrandados y paredes alveolares bien conservadas. La función del receptor del factor estimulante de colonias de granulocitos y macrófagos (GM-CSF) está alterada, pero los autoanticuerpos del receptor de GM-CSF están ausentes."},"it":{"name":"Proteinosi alveolare polmonare ereditaria","synonyms":["PAP congenita","Proteinosi alveolare polmonare congenita"],"definition":"Si tratta di una pneumopatia interstiziale genetica rara, causata da mutazioni nelle subunità alfa o beta di CSF2R (recettore del fattore 2 stimolante le colonie) e caratterizzata dall'accumulo di surfattante polmonare negli alveoli. Il quadro clinico è molto variabile; i pazienti possono essere asintomatici oppure presentare insufficienza respiratoria grave. In genere la biopsia polmonare evidenzia materiale eosinofilo granulare positivo alla reazione PAS, macrofagi alveolari schiumosi di dimensioni aumentate e pareti alveolari preservate. La funzione del recettore del fattore stimolante le colonie dei granulociti-macrofagi (GM-CSF) è compromessa, in assenza di autoanticorpi contro il recettore del GM-CSF."},"nl":{"name":"Erfelijke pulmonale alveolaire proteïnose","synonyms":["Congenitale PAP","Congenitale pulmonale alveolaire proteïnose"],"definition":"Een zeldzame, genetische interstitiële longziekte als gevolg van mutaties in alfa- of bèta-subeenheden van CSF2R (koloniestimulerende factor 2-receptor), gekarakteriseerd door accumulatie van longsurfactant in longblaasjes, wat zich presenteert met een zeer variabel klinisch beeld, gaande van asymptomatisch tot ernstig respiratoir falen. Typische bevindingen bij longbiopsie zijn onder meer positieve Schiff-perjoodzuurkleuring, granulair eosinofiel materiaal, vergrote, schuimige alveolaire macrofagen, en goed bewaarde alveolaire wanden. De functie van de receptor voor granulocyt-macrofaag koloniestimulerende factor (GM-CSF) is verstoord, maar auto-antilichamen tegen GM-CSF-receptor zijn afwezig."},"pt":{"name":"Proteinose congénita dos alvéolos pulmonares"},"pl":{"name":"Wrodzona proteinoza pęcherzyków płucnych","synonyms":["Wrodzona PAP"]},"cs":{"name":"Dědičná plicní alveolární proteinóza","synonyms":["Vrozená PAP","Vrozená plicní alveolární proteinóza"]},"uk":{"name":"Спадковий пульмонарний альвеолярний протеїноз","synonyms":["Вроджений PAP","Вроджений альвеолярний протеїноз легень"],"definition":"A rare, genetic, interstitial lung disease due to mutations in the CSF2R (colony-stimulating factor 2 receptor) alpha or beta subunits and characterized by alveolar accumulation of pulmonary surfactant, presenting a highly variable clinical presentation, ranging from asymptomatic to severe respiratory failure. Characteristic lung biopsy findings include periodic acid-Schiff-positive, granular eosinophilic material, enlarged foamy alveolar macrophages, and well-preserved alveolar walls. The Granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor function is impaired but GM-CSF receptor autoantibodies are absent."},"zh":{"name":"遗传性肺泡蛋白沉积症","synonyms":["先天性肺泡蛋白沉积症"],"definition":"一种罕见的遗传性间质性肺部疾病，由CSF2R(集落刺激因子2受体)α或β亚基突变引起，特征是肺表面活性物质在肺泡内堆积，临床表现多种多样，从无症状到严重呼吸衰竭。特征性的肺活检结果包括高碘酸席夫阳性、颗粒状嗜酸性物质、增大的泡沫状肺泡巨噬细胞和保存完好的肺泡壁。粒细胞-巨噬细胞集落刺激因子(GM-CSF)受体功能受损，但GM-CSF受体自身抗体缺失。"},"tr":{"name":"Kalıtsal pulmoner alveolar proteinoz","synonyms":["Doğumsal PAP","Doğumsal pulmoner alveolar proteinoz"]}},"xrefs":[{"source":"OMIM","code":"300770","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"614370","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"J84.0","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"CB04.31","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"1603032478"},{"source":"MONDO","code":"0012580","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"C535832","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C2931035","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"4582","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":97955,"name":"Rare respiratory disease"},"parents":[{"orpha":674896,"name":"Non-syndromic congenital phagocyte functional defect","classifications":[156,195]},{"orpha":100049,"name":"Primary interstitial lung disease specific to childhood due to pulmonary surfactant protein anomalies","classifications":[156,184,233]}],"children":[],"genes":[{"symbol":"CSF2RA","name":"colony stimulating factor 2 receptor subunit alpha","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"18955570[PMID]","hgnc":"2435","ensembl":"ENSG00000198223","omim":"306250","loci":["Xp22.32 and Yp11.3"]},{"symbol":"CSF2RB","name":"colony stimulating factor 2 receptor subunit beta","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"21075760[PMID]_21205713[PMID]","hgnc":"2436","ensembl":"ENSG00000100368","omim":"138981","loci":["22q12.3"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Adolescent","Adult","Childhood","Elderly","Infancy"],"prevalence":[{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_20622029[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2019-02-21","source":"28212655[PMID]_21075760[PMID]_9410898[PMID]_18955570[PMID]_18955567[PMID]","terms":[{"hpo":"HP:0010876","label":"Abnormal circulating protein level","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0025391","label":"Crazy paving pattern on pulmonary HRCT","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001531","label":"Failure to thrive in infancy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012418","label":"Hypoxemia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002098","label":"Respiratory distress","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004887","label":"Respiratory failure requiring assisted ventilation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002091","label":"Restrictive ventilatory defect","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011949","label":"Acute infectious pneumonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0030057","label":"Autoimmune antibody positivity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012735","label":"Cough","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0030830","label":"Crackles","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0031029","label":"Elevated carcinoembryonic antigen level","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003651","label":"Foam cells","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001649","label":"Tachycardia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002789","label":"Tachypnea","frequency":"Occasional (29-5%)","criteria":null}]}}