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Hereditary pulmonary alveolar proteinosis

MedGen UID:
777976
Concept ID:
C3711368
Disease or Syndrome
Synonym: Pulmonary surfactant metabolism dysfunction
SNOMED CT: Genetic disorder of surfactant dysfunction (328641000119109)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Related genes: SFTPC, SFTPB, CSF2RA, ABCA3
 
Monarch Initiative: MONDO:0012580
OMIM® Phenotypic series: PS265120
Orphanet: ORPHA264675

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. [from ORDO]

Professional guidelines

PubMed

Lettieri S, Bonella F, Marando VA, Franciosi AN, Corsico AG, Campo I
Eur Respir Rev 2024 Jul;33(173) Epub 2024 Aug 14 doi: 10.1183/16000617.0064-2024. PMID: 39142709Free PMC Article
McCarthy C, Kokosi M, Bonella F
Curr Opin Pulm Med 2019 Sep;25(5):450-458. doi: 10.1097/MCP.0000000000000601. PMID: 31365379

Recent clinical studies

Etiology

Papiris SA, Tsirigotis P, Kolilekas L, Papadaki G, Papaioannou AI, Triantafillidou C, Papaporfyriou A, Karakatsani A, Kagouridis K, Griese M, Manali ED
Expert Rev Respir Med 2015 Jun;9(3):337-49. Epub 2015 Apr 12 doi: 10.1586/17476348.2015.1035259. PMID: 25864717

Diagnosis

Schmidt A, Kenia P, Morgan C, Bush A
Pediatr Pulmonol 2021 Jun;56(6):1687-1689. Epub 2021 Mar 8 doi: 10.1002/ppul.25336. PMID: 33629535
Chiu CY, Su SC, Fan WL, Lai SH, Tsai MH, Chen SH, Wong KS, Chung WH
Sci Rep 2017 Feb 24;7:43469. doi: 10.1038/srep43469. PMID: 28233860Free PMC Article
Ito M, Nakagome K, Ohta H, Akasaka K, Uchida Y, Hashimoto A, Shiono A, Takada T, Nagata M, Tohyama J, Hagiwara K, Kanazawa M, Nakata K, Tazawa R
BMC Pulm Med 2017 Feb 17;17(1):40. doi: 10.1186/s12890-017-0382-x. PMID: 28212655Free PMC Article
Tanaka T, Motoi N, Tsuchihashi Y, Tazawa R, Kaneko C, Nei T, Yamamoto T, Hayashi T, Tagawa T, Nagayasu T, Kuribayashi F, Ariyoshi K, Nakata K, Morimoto K
J Med Genet 2011 Mar;48(3):205-9. Epub 2010 Nov 12 doi: 10.1136/jmg.2010.082586. PMID: 21075760
Suzuki T, Sakagami T, Young LR, Carey BC, Wood RE, Luisetti M, Wert SE, Rubin BK, Kevill K, Chalk C, Whitsett JA, Stevens C, Nogee LM, Campo I, Trapnell BC
Am J Respir Crit Care Med 2010 Nov 15;182(10):1292-304. Epub 2010 Jul 9 doi: 10.1164/rccm.201002-0271OC. PMID: 20622029Free PMC Article

Therapy

Beeckmans H, Ambrocio GPL, Bos S, Vermaut A, Geudens V, Vanstapel A, Vanaudenaerde BM, De Baets F, Malfait TLA, Emonds MP, Van Raemdonck DE, Schoemans HM, Vos R
Front Immunol 2022;13:931153. Epub 2022 Jul 14 doi: 10.3389/fimmu.2022.931153. PMID: 35928826Free PMC Article
Hetzel M, Suzuki T, Hashtchin AR, Arumugam P, Carey B, Schwabbauer M, Kuhn A, Meyer J, Schambach A, Van Der Loo J, Moritz T, Trapnell BC, Lachmann N
Hum Gene Ther Methods 2017 Dec;28(6):318-329. Epub 2017 Aug 30 doi: 10.1089/hgtb.2017.092. PMID: 28854814Free PMC Article
Papiris SA, Tsirigotis P, Kolilekas L, Papadaki G, Papaioannou AI, Triantafillidou C, Papaporfyriou A, Karakatsani A, Kagouridis K, Griese M, Manali ED
Expert Rev Respir Med 2015 Jun;9(3):337-49. Epub 2015 Apr 12 doi: 10.1586/17476348.2015.1035259. PMID: 25864717
Lachmann N, Happle C, Ackermann M, Lüttge D, Wetzke M, Merkert S, Hetzel M, Kensah G, Jara-Avaca M, Mucci A, Skuljec J, Dittrich AM, Pfaff N, Brennig S, Schambach A, Steinemann D, Göhring G, Cantz T, Martin U, Schwerk N, Hansen G, Moritz T
Am J Respir Crit Care Med 2014 Jan 15;189(2):167-82. doi: 10.1164/rccm.201306-1012OC. PMID: 24279725

Prognosis

Shima K, Arumugam P, Sallese A, Horio Y, Ma Y, Trapnell C, Wessendarp M, Chalk C, McCarthy C, Carey BC, Trapnell BC, Suzuki T
Am J Physiol Lung Cell Mol Physiol 2022 Mar 1;322(3):L438-L448. Epub 2022 Jan 19 doi: 10.1152/ajplung.00175.2021. PMID: 35043685Free PMC Article

Clinical prediction guides

Ito M, Nakagome K, Ohta H, Akasaka K, Uchida Y, Hashimoto A, Shiono A, Takada T, Nagata M, Tohyama J, Hagiwara K, Kanazawa M, Nakata K, Tazawa R
BMC Pulm Med 2017 Feb 17;17(1):40. doi: 10.1186/s12890-017-0382-x. PMID: 28212655Free PMC Article
Happle C, Lachmann N, Škuljec J, Wetzke M, Ackermann M, Brennig S, Mucci A, Jirmo AC, Groos S, Mirenska A, Hennig C, Rodt T, Bankstahl JP, Schwerk N, Moritz T, Hansen G
Sci Transl Med 2014 Aug 20;6(250):250ra113. doi: 10.1126/scitranslmed.3009750. PMID: 25143363
Tanaka T, Motoi N, Tsuchihashi Y, Tazawa R, Kaneko C, Nei T, Yamamoto T, Hayashi T, Tagawa T, Nagayasu T, Kuribayashi F, Ariyoshi K, Nakata K, Morimoto K
J Med Genet 2011 Mar;48(3):205-9. Epub 2010 Nov 12 doi: 10.1136/jmg.2010.082586. PMID: 21075760

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