{"Name":"Hereditary pulmonary alveolar proteinosis","DiseaseID__c":"GARD:0004582","id":4582,"encodedName":"hereditary-pulmonary-alveolar-proteinosis","IsDeleted":false,"Disease_Name_Full__c":"Hereditary pulmonary alveolar proteinosis","Xref_IDs__c":"707442002; C3711368; C535832; MEDGEN:777976; MONDO:0012580; OMIMPS:265120; ORPHA:264675","USA_Estimate__c":"1,000","No_of_Specialist_Tagsa__c":4,"No_of_ClinGen_records__c":0,"No_of_GeneReviews__c":0,"No_of_HHS_records__c":1,"World_Estimate__c":"1 to 8,000","No_of_HRSA_records__c":0,"Evidence_Based_Score__c":1,"No_of_Disease_Descriptions__c":4,"Disease_Characteristics_Score__c":8,"No_of_Age_at_Onset__c":5,"Description_Source__c":"MONDO:0012580","Disease_Description__c":"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.","GARD_Name__c":"Hereditary pulmonary alveolar proteinosis","GARD_Synonym__c":"congenital pap; congenital pulmonary alveolar proteinosis; genetic disorder of surfactant dysfunction; inborn error of pulmonary surfactant metabolism; inborn error of surfactant metabolism; pulmonary surfactant metabolism dysfunction","Curated_Disease_Description_Source__c":"GARD:0004582","Curated_Disease_Description__c":"Hereditary pulmonary alveolar proteinosis is a rare form of respiratory failure that is present from birth. In this condition, a substance made up of fat and protein (surfactant) builds up in the air sacs (alveoli) of the lungs, making breathing difficult. Hereditary pulmonary alveolar proteinosis is caused by genetic changes in one of several different genes. It is inherited in either an autosomal dominant, autosomal recessive or X-linked recessive pattern depending on the gene involved. If the gene involved is the ABCA3 gene, the CSF2RB gene, or the SFTPB gene, inheritance is autosomal recessive. If the gene involved is the SFTPC gene, inheritance is autosomal dominant. If the gene involved is the CSF2RA gene, inheritance is X-linked recessive. Hereditary pulmonary alveolar proteinosis is diagnosed based on the symptoms, imaging studies and genetic testing.","Curated_USA_Estimate_Source__c":null,"Curated_USA_Estimate__c":"1,000","Age_at_Onset_Snippet_Text__c":"at a variety of ages","SourceID__c":"ORPHA:264675","Deprecated__c":"No","Disease_Concept_Type__c":"Rare Disease Grouping","MONDO_ID__c":"MONDO:0012580","ORPHANET_ID__c":"ORPHA:264675","Replaced_By_ID__c":null,"Display_Spanish_Disease_Name__c":"Proteinosis alveolar pulmonar hereditaria","Spanish_Description_Source__c":"ORPHA:264675","Spanish_Description__c":"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.","Spanish_Disease_Name__c":"proteinosis alveolar pulmonar hereditaria","Spanish_GARD_Synonym__c":"pap congénita; proteinosis alveolar pulmonar congénita","Category_Linearization__c":"ORPHA:97955","icd10_id__c":null,"mesh_id__c":null,"omim_id__c":null,"snomed_id__c":null,"umls_id__c":null,"GARD_Disease__c":[{"Curated_Disease_Description__c":"Hereditary pulmonary alveolar proteinosis is a rare form of respiratory failure that is present from birth. In this condition, a substance made up of fat and protein (surfactant) builds up in the air sacs (alveoli) of the lungs, making breathing difficult. Hereditary pulmonary alveolar proteinosis is caused by genetic changes in one of several different genes. It is inherited in either an autosomal dominant, autosomal recessive or X-linked recessive pattern depending on the gene involved. If the gene involved is the ABCA3 gene, the CSF2RB gene, or the SFTPB gene, inheritance is autosomal recessive. If the gene involved is the SFTPC gene, inheritance is autosomal dominant. If the gene involved is the CSF2RA gene, inheritance is X-linked recessive. Hereditary pulmonary alveolar proteinosis is diagnosed based on the symptoms, imaging studies and genetic testing.","Curated_Disease_Description_Source__c":"GARD:0004582","GARD_Synonym__c":"congenital pap; congenital pulmonary alveolar proteinosis; genetic disorder of surfactant dysfunction; inborn error of pulmonary surfactant metabolism; inborn error of surfactant metabolism; pulmonary surfactant metabolism dysfunction","Name":"Hereditary pulmonary alveolar proteinosis","Curated_USA_Estimate__c":"1,000","estimateUsa":"1,000"}],"Organization_Supported_Diseases__c":[{"Account_Name__c":"Alianza Iberoamericana de Enfermedades Raras o Poco Frecuentes","Website__c":"https://aliber.org/web/"},{"Account_Name__c":"Federación Mexicana de Enfermedades Raras (FEMEXER)","Website__c":"http://www.femexer.org/"},{"Account_Name__c":"Federación Española de Enfermedades Raras","Website__c":"https://enfermedades-raras.org/"},{"Account_Name__c":"Federación Colombiana de Enfermedades Raras","Website__c":"http://www.fecoer.org"},{"Account_Name__c":"Federación Argentina de Enfermedades Poco Frecuentes","Website__c":"https://fadepof.org.ar/"},{"Account_Name__c":"Asociación Todos Unidos Enfermedades Raras Uruguay","Website__c":"https://atueru.org.uy/"},{"Account_Name__c":"The PAP Foundation","Website__c":"https://www.papfoundation.org/"},{"Account_Name__c":"Children's Interstitial Lung Disease Foundation","Website__c":"https://child-foundation.org/"}],"GARD_Disease_Tag__c":[{"Tag_Name__c":"Genetics","Tag_Category__c":"Cause;Disease Category;Specialist","category_description":"Genetic diseases affect the DNA, or genetic instructions, which directs how tissues, organs, and body systems function.","curated_tag_name":"Genetic diseases"},{"Tag_Name__c":"Pulmonology","Tag_Category__c":"Disease Category;Specialist","category_description":"Respiratory diseases affect the nose, mouth, throat, voice box, windpipe, lungs, or blood vessels.","curated_tag_name":"Respiratory diseases"},{"Tag_Name__c":"Immunology","Tag_Category__c":"Specialist"},{"Tag_Name__c":"Primary Immune Deficiencies","Tag_Category__c":"Account","curated_tag_name":"Primary immunodeficiency"},{"Tag_Name__c":"Pediatrics","Tag_Category__c":"Specialist"}],"Age_At_Onset__c":[{"Age_At_Onset__c":"Adolescent","Provided_By__c":"ORPHA:264675"},{"Age_At_Onset__c":"Elderly","Provided_By__c":"ORPHA:264675"},{"Age_At_Onset__c":"Adult","Provided_By__c":"ORPHA:264675"},{"Age_At_Onset__c":"Infancy","Provided_By__c":"ORPHA:264675"},{"Age_At_Onset__c":"Childhood","Provided_By__c":"ORPHA:264675"}],"External_Identifier_Disease__c":[{"URL__c":"https://raresource.nih.gov/diseases/filter/0004582","Source__c":"RareSource"},{"URL__c":"https://www.ncbi.nlm.nih.gov/mesh/C535832","Source__c":"MONDO:0012580","Xref__c":"C535832"},{"URL__c":"https://www.ncbi.nlm.nih.gov/medgen/?term=777976","Source__c":"C3711368","Xref__c":"MEDGEN:777976"},{"URL__c":"https://www.omim.org/phenotypicSeries/PS265120","Source__c":"MONDO:0012580","Xref__c":"OMIMPS:265120"},{"URL__c":"https://browser.ihtsdotools.org/?perspective=full&conceptId1=707442002","Source__c":"MONDO:0012580","Xref__c":"707442002"},{"URL__c":"https://uts.nlm.nih.gov/uts/umls/concept/C3711368","Source__c":"C3711368","Xref__c":"C3711368"},{"URL__c":"https://www.orpha.net/en/disease/detail/264675","Source__c":"C3711368; MONDO:0012580","Xref__c":"ORPHA:264675"},{"URL__c":"https://browser.ihtsdotools.org/?perspective=full&conceptId1=328641000119109","Source__c":"C3711368","Xref__c":"328641000119109"},{"URL__c":"http://purl.obolibrary.org/obo/MONDO_0012580","Source__c":"GARD:0004582","Xref__c":"MONDO:0012580"},{"URL__c":"https://medlineplus.gov/genetics/condition/surfactant-dysfunction","Source__c":"GARD:0004582","Xref__c":"https://medlineplus.gov/genetics/condition/surfactant-dysfunction"}],"GARD_Disease_Gene__c":[{"GeneSymbol__c":"CSF2RB","Gene_Type__c":"protein-coding gene","Causal_Gene__c":true},{"GeneSymbol__c":"CSF2RA","Gene_Type__c":"protein-coding gene","Causal_Gene__c":true}],"Inheritance__c":["Autosomal recessive"],"GARD_Disease_Feature__c":[{"Provided_By__c":"ORPHA:264675","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"An abnormally low level of blood oxygen.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0012418","HPO_Synonym__c":"Low blood oxygen level","HPO_Name__c":"Hypoxemia","Feature_System__c":"Respiratory system","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:264675","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"An abnormal level of a circulating protein in the blood.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0010876","HPO_Synonym__c":"Abnormal circulating protein level; Abnormality of circulating protein level","HPO_Name__c":"Abnormal circulating protein concentration","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"ORPHA:264675","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"The presence of an antibody in the blood circulation that is directed against the organism's own cells or tissues.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0030057","HPO_Name__c":"Autoimmune antibody positivity","Feature_System__c":"Immune System","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"ORPHA:264675","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"The concentration of CEA (carcinoembryonic antigen) in the blood circulation is above the upper limit of normal.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0031029","HPO_Synonym__c":"Elevated carcinoembryonic antigen level; Increased plasma CEA","HPO_Name__c":"Elevated circulating CEA concentration","HPO_Feature_Type__c":"Lab"}},{"Provided_By__c":"ORPHA:264675","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Crackles are discontinuous, explosive, and nonmusical adventitious lung sounds normally heard in inspiration and sometimes during expiration. Crackles are usually classified as fine and coarse crackles based on their duration, loudness, pitch, timing in the respiratory cycle, and relationship to coughing and changing body position.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0030830","HPO_Synonym__c":"Crepitations; Rales","HPO_Name__c":"Crackles","Feature_System__c":"Respiratory system","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:264675","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Respiratory distress is objectively observable as the physical or emotional consequences from the experience of dyspnea. The physical presentation of respiratory distress is generally referred to as labored breathing, while the sensation of respiratory distress is called shortness of breath or dyspnea.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002098","HPO_Synonym__c":"Breathing difficulties; Labored breathing; Respiratory difficulties","HPO_Name__c":"Respiratory distress","Feature_System__c":"Respiratory system","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:264675","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"The so-called crazy paving pattern appears as thickened interlobular septa and intralobular lines superimposed on a background of ground-glass opacity, resembling irregularly shaped paving stones. The crazy-paving pattern is often sharply demarcated from more normal lung and may have a geographic outline. It was originally reported in patients with alveolar proteinosis and is also encountered in other diffuse lung diseases that affect both the interstitial and airspace compartments, such as lipoid pneumonia.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0025391","HPO_Synonym__c":"Crazy paving pattern on pulmonary HRCT; Crazy-paving pattern","HPO_Name__c":"Crazy paving pattern","Feature_System__c":"Respiratory system","HPO_Feature_Type__c":"Imaging_CT"}},{"Provided_By__c":"ORPHA:264675","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001531","HPO_Synonym__c":"Failure to thrive in first year of life; Faltering weight in infancy; Weight faltering in infancy","HPO_Name__c":"Failure to thrive in infancy","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:264675","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Acute inflammation of the lung due to an infection.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0011949","HPO_Name__c":"Acute infectious pneumonia","Feature_System__c":"Respiratory system; Immune System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:264675","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"The presence of foam cells, a type of macrophage that localizes to fatty deposits on blood vessel walls, where they ingest low-density lipoproteins and become laden with lipids, giving them a foamy appearance.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0003651","HPO_Synonym__c":"Foamy histiocytes; Foamy macrophages; Lipid-laden histiocytes; Presence of foam cells","HPO_Name__c":"Foam cells","Feature_System__c":"Cardiovascular System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:264675","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"A sudden, audible expulsion of air from the lungs through a partially closed glottis, preceded by inhalation.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0012735","HPO_Synonym__c":"Cough; Coughing","HPO_Name__c":"Cough","Feature_System__c":"Respiratory system","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:264675","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"A functional defect characterized by reduced total lung capacity (TLC) not associated with abnormalities of expiratory airflow or airway resistance. Spirometrically, a restrictive defect is defined as FEV1 (forced expiratory volume in 1 second) and FVC (forced vital capacity) less than 80 per cent. Restrictive lung disease may be caused by alterations in lung parenchyma or because of a disease of the pleura, chest wall, or neuromuscular apparatus.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002091","HPO_Synonym__c":"Restrictive deficit on pulmonary function testing; Restrictive deficit on pulmonary function tests; Restrictive respiratory disease; Restrictive respiratory insufficiency; Restrictive respiratory syndrome; Spirometric restriction; Stiff lung or chest wall causing decreased lung volume","HPO_Name__c":"Restrictive ventilatory defect","Feature_System__c":"Respiratory system","HPO_Feature_Type__c":"Procedure_PFT"}},{"Provided_By__c":"ORPHA:264675","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"A state of respiratory distress that requires a life saving intervention in the form of gaining airway access and instituting positive pressure ventilation.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0004887","HPO_Synonym__c":"Respiratory distress necessitating mechanical ventilation; Respiratory distress requiring endotracheal intubation; Respiratory distress requiring mechanical ventilation","HPO_Name__c":"Respiratory failure requiring assisted ventilation","Feature_System__c":"Respiratory system","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:264675","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"A rapid heartrate that exceeds the range of the normal resting heartrate for age.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001649","HPO_Synonym__c":"Fast heart rate; Heart racing; Racing heart","HPO_Name__c":"Tachycardia","Feature_System__c":"Cardiovascular System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:264675","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Very rapid breathing.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002789","HPO_Synonym__c":"Increased respiratory rate or depth of breathing; Polypnea","HPO_Name__c":"Tachypnea","Feature_System__c":"Respiratory system","HPO_Feature_Type__c":"Symptom"}}],"tags":{"Cause":["Genetics"],"Disease Category":["Genetics","Pulmonology"],"Specialist":["Genetics","Pulmonology","Immunology","Pediatrics"],"Account":["Primary Immune Deficiencies"]},"synonyms":["congenital pap"," congenital pulmonary alveolar proteinosis"," genetic disorder of surfactant dysfunction"," inborn error of pulmonary surfactant metabolism"," inborn error of surfactant metabolism"," pulmonary surfactant metabolism dysfunction"],"spanishId":13755,"spanishName":"proteinosis-alveolar-pulmonar-congenita"}