Advertisement

Other Diffuse Lung Diseases: Diffuse Cystic Lung Diseases (LAM, TSC, BHD), Sarcoidosis, Pulmonary Alveolar Proteinosis, and Pulmonary Alveolar Microlithiasis—What Are the Roles of Genetic Factors in the Pathogenesis of These Diseases?

  • Haruhiko Furusawa
  • Masahiro Masuo
  • Yoshihisa Nukui
  • Yasunari Miyazaki
  • Naohiko Inase
Chapter
Part of the Respiratory Disease Series: Diagnostic Tools and Disease Managements book series (RDSDTDM)

Abstract

Lymphangioleiomyomatosis (LAM) is a rare multisystem disorder that mostly affects women in their reproductive years and predominantly affects the lungs. LAM occurs in patients with tuberous sclerosis complex (TSC-LAM) and as a sporadic form in patients who do not have tuberous sclerosis (S-LAM). Patients with TSC-LAM have germline mutations either in TSC1 located on chromosome 9q34 or TSC2 located on chromosome 16p13.3, and the majority have a germline mutation in TCS2.

Birt-Hogg-Dubé (BHD) syndrome is a rare autosomal dominant disorder that is characterized by the development of cutaneous fibrofolliculomas, renal tumors, and pulmonary cysts, causing spontaneous pneumothorax. BHD is caused by germline mutations in the folliculin (FLCN) gene on chromosome 17 (17p12q11.2), which encodes the protein FLCN.

Sarcoidosis is a systemic granulomatous disease that affects young and middle-aged adults. It frequently presents with bilateral hilar lymphadenopathy, pulmonary infiltration, and ocular and skin lesions. Granuloma formation is caused by T-cell activation by antigen presentation; therefore, the most prominent finding was a linkage to a section within human leukocyte antigens (HLA), a linkage to HLA-DRB1-alleles, and variants of these alleles are associated with the disease course and specific organ involvement.

Pulmonary alveolar proteinosis (PAP) is a rare disease in which surfactants mainly accumulate in the alveolar space due to the dysregulation of surfactant clearance by AMs. GM-CSF receptor gene mutations, surfactant-related genes SFTPB and SFTPC, gene mutations in ATP-binding cassette 3 (ABCA3), which is essential for the intracellular transport of surfactant, and NK2 homeobox 1 (NKX2-1), which is essential for the development of alveolar epithelial cells, have been reported in PAP patients.

Pulmonary alveolar microlithiasis (PAM) is an extremely rare disease and an autosomal recessive genetic disorder. Inactivating mutations are present in the solute carrier family 34 member 2 (SLC34A2) gene, which encodes the Ilb type sodium-dependent phosphoryl transport protein.

Keywords

Lymphangioleiomyomatosis TSC Birt-Hogg-Dubé syndrome FLCN Sarcoidosis HLA-DRB1 Pulmonary alveolar proteinosis GM-CSF receptor SFTPB SFTPC ABCA3 NKX2-1 Pulmonary alveolar microlithiasis SLC34A2 

References

  1. 1.
    McCormack FX. Lymphangioleiomyomatosis: a clinical update. Chest. 2008;133(2):507–16.  https://doi.org/10.1378/chest.07-0898.CrossRefPubMedGoogle Scholar
  2. 2.
    Gupta N, Vassallo R, Wikenheiser-Brokamp KA, McCormack FX. Diffuse Cystic Lung Disease. Part I. Am J Respir Crit Care Med. 2015;191(12):1354–66.  https://doi.org/10.1164/rccm.201411-2094CI.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Crino PB, Nathanson KL, Henske EP. The tuberous sclerosis complex. N Engl J Med. 2006;355(13):1345–56.  https://doi.org/10.1056/NEJMra055323.CrossRefPubMedGoogle Scholar
  4. 4.
    Harknett EC, Chang WY, Byrnes S, Johnson J, Lazor R, Cohen MM, et al. Use of variability in national and regional data to estimate the prevalence of lymphangioleiomyomatosis. QJM. 2011;104(11):971–9.  https://doi.org/10.1093/qjmed/hcr116.CrossRefPubMedGoogle Scholar
  5. 5.
    Adriaensen ME, Schaefer-Prokop CM, Duyndam DA, Zonnenberg BA, Prokop M. Radiological evidence of lymphangioleiomyomatosis in female and male patients with tuberous sclerosis complex. Clin Radiol. 2011;66(7):625–8.  https://doi.org/10.1016/j.crad.2011.02.009.CrossRefPubMedGoogle Scholar
  6. 6.
    Schiavina M, Di Scioscio V, Contini P, Cavazza A, Fabiani A, Barberis M, et al. Pulmonary lymphangioleiomyomatosis in a karyotypically normal man without tuberous sclerosis complex. Am J Respir Crit Care Med. 2007;176(1):96–8.  https://doi.org/10.1164/rccm.200610-1408CR.CrossRefPubMedGoogle Scholar
  7. 7.
    Johnson SR, Whale CI, Hubbard RB, Lewis SA, Tattersfield AE. Survival and disease progression in UK patients with lymphangioleiomyomatosis. Thorax. 2004;59(9):800–3.  https://doi.org/10.1136/thx.2004.023283.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Hayashida M, Yasuo M, Hanaoka M, Seyama K, Inoue Y, Tatsumi K, et al. Reductions in pulmonary function detected in patients with lymphangioleiomyomatosis: an analysis of the Japanese National Research Project on Intractable Diseases database. Respir Investig. 2016;54(3):193–200.  https://doi.org/10.1016/j.resinv.2015.11.003.CrossRefPubMedGoogle Scholar
  9. 9.
    Taveira-DaSilva AM, Hedin C, Stylianou MP, Travis WD, Matsui K, Ferrans VJ, et al. Reversible airflow obstruction, proliferation of abnormal smooth muscle cells, and impairment of gas exchange as predictors of outcome in lymphangioleiomyomatosis. Am J Respir Crit Care Med. 2001;164(6):1072–6.  https://doi.org/10.1164/ajrccm.164.6.2102125.CrossRefPubMedGoogle Scholar
  10. 10.
    Taveira-DaSilva AM, Pacheco-Rodriguez G, Moss J. The natural history of lymphangioleiomyomatosis: markers of severity, rate of progression and prognosis. Lymphat Res Biol. 2010;8(1):9–19.  https://doi.org/10.1089/lrb.2009.0024.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Ryu JH, Moss J, Beck GJ, Lee JC, Brown KK, Chapman JT, et al. The NHLBI lymphangioleiomyomatosis registry: characteristics of 230 patients at enrollment. Am J Respir Crit Care Med. 2006;173(1):105–11.  https://doi.org/10.1164/rccm.200409-1298OC.CrossRefPubMedGoogle Scholar
  12. 12.
    Tobino K, Johkoh T, Fujimoto K, Sakai F, Arakawa H, Kurihara M, et al. Computed tomographic features of lymphangioleiomyomatosis: evaluation in 138 patients. Eur J Radiol. 2015;84(3):534–41.  https://doi.org/10.1016/j.ejrad.2014.12.008.CrossRefPubMedGoogle Scholar
  13. 13.
    Lenoir S, Grenier P, Brauner MW, Frija J, Remy-Jardin M, Revel D, et al. Pulmonary lymphangiomyomatosis and tuberous sclerosis: comparison of radiographic and thin-section CT findings. Radiology. 1990;175(2):329–34.  https://doi.org/10.1148/radiology.175.2.2326456.CrossRefPubMedGoogle Scholar
  14. 14.
    Johnson SR, Cordier JF, Lazor R, Cottin V, Costabel U, Harari S, et al. European Respiratory Society guidelines for the diagnosis and management of lymphangioleiomyomatosis. Eur Respir J. 2010;35(1):14–26.  https://doi.org/10.1183/09031936.00076209.CrossRefPubMedGoogle Scholar
  15. 15.
    Ferrans VJ, Yu ZX, Nelson WK, Valencia JC, Tatsuguchi A, Avila NA, et al. Lymphangioleiomyomatosis (LAM): a review of clinical and morphological features. J Nippon Med Sch. 2000;67(5):311–29.CrossRefGoogle Scholar
  16. 16.
    Matsumoto Y, Horiba K, Usuki J, Chu SC, Ferrans VJ, Moss J. Markers of cell proliferation and expression of melanosomal antigen in lymphangioleiomyomatosis. Am J Respir Cell Mol Biol. 1999;21(3):327–36.  https://doi.org/10.1165/ajrcmb.21.3.3693.CrossRefPubMedGoogle Scholar
  17. 17.
    Gao L, Yue MM, Davis J, Hyjek E, Schuger L. In pulmonary lymphangioleiomyomatosis expression of progesterone receptor is frequently higher than that of estrogen receptor. Virchows Arch. 2014;464(4):495–503.  https://doi.org/10.1007/s00428-014-1559-9.CrossRefPubMedGoogle Scholar
  18. 18.
    Kumasaka T, Seyama K, Mitani K, Sato T, Souma S, Kondo T, et al. Lymphangiogenesis in lymphangioleiomyomatosis: its implication in the progression of lymphangioleiomyomatosis. Am J Surg Pathol. 2004;28(8):1007–16.CrossRefGoogle Scholar
  19. 19.
    Young LR, Vandyke R, Gulleman PM, Inoue Y, Brown KK, Schmidt LS, et al. Serum vascular endothelial growth factor-D prospectively distinguishes lymphangioleiomyomatosis from other diseases. Chest. 2010;138(3):674–81.  https://doi.org/10.1378/chest.10-0573.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    van Slegtenhorst M, de Hoogt R, Hermans C, Nellist M, Janssen B, Verhoef S, et al. Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. Science. 1997;277(5327):805–8.CrossRefGoogle Scholar
  21. 21.
    European Chromosome 16 Tuberous Sclerosis C. Identification and characterization of the tuberous sclerosis gene on chromosome 16. Cell. 1993;75(7):1305–15.CrossRefGoogle Scholar
  22. 22.
    Strizheva GD, Carsillo T, Kruger WD, Sullivan EJ, Ryu JH, Henske EP. The spectrum of mutations in TSC1 and TSC2 in women with tuberous sclerosis and lymphangiomyomatosis. Am J Respir Crit Care Med. 2001;163(1):253–8.  https://doi.org/10.1164/ajrccm.163.1.2005004.CrossRefPubMedGoogle Scholar
  23. 23.
    Astrinidis A, Khare L, Carsillo T, Smolarek T, Au KS, Northrup H, et al. Mutational analysis of the tuberous sclerosis gene TSC2 in patients with pulmonary lymphangioleiomyomatosis. J Med Genet. 2000;37(1):55–7.CrossRefGoogle Scholar
  24. 24.
    Smolarek TA, Wessner LL, McCormack FX, Mylet JC, Menon AG, Henske EP. Evidence that lymphangiomyomatosis is caused by TSC2 mutations: chromosome 16p13 loss of heterozygosity in angiomyolipomas and lymph nodes from women with lymphangiomyomatosis. Am J Hum Genet. 1998;62(4):810–5.  https://doi.org/10.1086/301804.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Yu J, Astrinidis A, Henske EP. Chromosome 16 loss of heterozygosity in tuberous sclerosis and sporadic lymphangiomyomatosis. Am J Respir Crit Care Med. 2001;164(8 Pt 1):1537–40.  https://doi.org/10.1164/ajrccm.164.8.2104095.CrossRefPubMedGoogle Scholar
  26. 26.
    Carsillo T, Astrinidis A, Henske EP. Mutations in the tuberous sclerosis complex gene TSC2 are a cause of sporadic pulmonary lymphangioleiomyomatosis. Proc Natl Acad Sci U S A. 2000;97(11):6085–90.CrossRefGoogle Scholar
  27. 27.
    Badri KR, Gao L, Hyjek E, Schuger N, Schuger L, Qin W, et al. Exonic mutations of TSC2/TSC1 are common but not seen in all sporadic pulmonary lymphangioleiomyomatosis. Am J Respir Crit Care Med. 2013;187(6):663–5.  https://doi.org/10.1164/ajrccm.187.6.663.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Ito N, Rubin GM. gigas, a Drosophila homolog of tuberous sclerosis gene product-2, regulates the cell cycle. Cell. 1999;96(4):529–39.CrossRefGoogle Scholar
  29. 29.
    Tapon N, Ito N, Dickson BJ, Treisman JE, Hariharan IK. The Drosophila tuberous sclerosis complex gene homologs restrict cell growth and cell proliferation. Cell. 2001;105(3):345–55.CrossRefGoogle Scholar
  30. 30.
    Sengupta S, Peterson TR, Sabatini DM. Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress. Mol Cell. 2010;40(2):310–22.  https://doi.org/10.1016/j.molcel.2010.09.026.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    McCormack FX, Inoue Y, Moss J, Singer LG, Strange C, Nakata K, et al. Efficacy and safety of sirolimus in lymphangioleiomyomatosis. N Engl J Med. 2011;364(17):1595–606.  https://doi.org/10.1056/NEJMoa1100391.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    McCormack FX, Gupta N, Finlay GR, Young LR, Taveira-DaSilva AM, Glasgow CG, et al. Official American Thoracic Society/Japanese Respiratory Society clinical practice guidelines: lymphangioleiomyomatosis diagnosis and management. Am J Respir Crit Care Med. 2016;194(6):748–61.  https://doi.org/10.1164/rccm.201607-1384ST.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Almoosa KF, Ryu JH, Mendez J, Huggins JT, Young LR, Sullivan EJ, et al. Management of pneumothorax in lymphangioleiomyomatosis: effects on recurrence and lung transplantation complications. Chest. 2006;129(5):1274–81.  https://doi.org/10.1378/chest.129.5.1274.CrossRefPubMedGoogle Scholar
  34. 34.
    Boehler A, Speich R, Russi EW, Weder W. Lung transplantation for lymphangioleiomyomatosis. N Engl J Med. 1996;335(17):1275–80.  https://doi.org/10.1056/nejm199610243351704.CrossRefPubMedGoogle Scholar
  35. 35.
    Birt AR, Hogg GR, Dube WJ. Hereditary multiple fibrofolliculomas with trichodiscomas and acrochordons. Arch Dermatol. 1977;113(12):1674–7.CrossRefGoogle Scholar
  36. 36.
    Dal Sasso AA, Belem LC, Zanetti G, Souza CA, Escuissato DL, Irion KL, et al. Birt-Hogg-Dube syndrome. State-of-the-art review with emphasis on pulmonary involvement. Respir Med. 2015;109(3):289–96.  https://doi.org/10.1016/j.rmed.2014.11.008.CrossRefPubMedGoogle Scholar
  37. 37.
    Gupta N, Seyama K, McCormack FX. Pulmonary manifestations of Birt-Hogg-Dube syndrome. Fam Cancer. 2013;12(3):387–96.  https://doi.org/10.1007/s10689-013-9660-9.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Toro JR, Pautler SE, Stewart L, Glenn GM, Weinreich M, Toure O, et al. Lung cysts, spontaneous pneumothorax, and genetic associations in 89 families with Birt-Hogg-Dube syndrome. Am J Respir Crit Care Med. 2007;175(10):1044–53.  https://doi.org/10.1164/rccm.200610-1483OC.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Furuya M, Tanaka R, Koga S, Yatabe Y, Gotoda H, Takagi S, et al. Pulmonary cysts of Birt-Hogg-Dube syndrome: a clinicopathologic and immunohistochemical study of 9 families. Am J Surg Pathol. 2012;36(4):589–600.  https://doi.org/10.1097/PAS.0b013e3182475240.CrossRefPubMedGoogle Scholar
  40. 40.
    Kumasaka T, Hayashi T, Mitani K, Kataoka H, Kikkawa M, Tobino K, et al. Characterization of pulmonary cysts in Birt-Hogg-Dube syndrome: histopathological and morphometric analysis of 229 pulmonary cysts from 50 unrelated patients. Histopathology. 2014;65(1):100–10.  https://doi.org/10.1111/his.12368.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Schmidt LS, Linehan WM. Molecular genetics and clinical features of Birt-Hogg-Dube syndrome. Nat Rev Urol. 2015;12(10):558–69.  https://doi.org/10.1038/nrurol.2015.206.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Vocke CD, Yang Y, Pavlovich CP, Schmidt LS, Nickerson ML, Torres-Cabala CA, et al. High frequency of somatic frameshift BHD gene mutations in Birt-Hogg-Dube-associated renal tumors. J Natl Cancer Inst. 2005;97(12):931–5.  https://doi.org/10.1093/jnci/dji154.CrossRefPubMedGoogle Scholar
  43. 43.
    Khoo SK, Bradley M, Wong FK, Hedblad MA, Nordenskjold M, Teh BT. Birt-Hogg-Dube syndrome: mapping of a novel hereditary neoplasia gene to chromosome 17p12-q11.2. Oncogene. 2001;20(37):5239–42.  https://doi.org/10.1038/sj.onc.1204703.CrossRefPubMedGoogle Scholar
  44. 44.
    Schmidt LS, Warren MB, Nickerson ML, Weirich G, Matrosova V, Toro JR, et al. Birt-Hogg-Dube syndrome, a genodermatosis associated with spontaneous pneumothorax and kidney neoplasia, maps to chromosome 17p11.2. Am J Hum Genet. 2001;69(4):876–82.  https://doi.org/10.1086/323744.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Nickerson ML, Warren MB, Toro JR, Matrosova V, Glenn G, Turner ML, et al. Mutations in a novel gene lead to kidney tumors, lung wall defects, and benign tumors of the hair follicle in patients with the Birt-Hogg-Dube syndrome. Cancer Cell. 2002;2(2):157–64.CrossRefGoogle Scholar
  46. 46.
    Kennedy JC, Khabibullin D, Henske EP. Mechanisms of pulmonary cyst pathogenesis in Birt-Hogg-Dube syndrome: the stretch hypothesis. Semin Cell Dev Biol. 2016;52:47–52.  https://doi.org/10.1016/j.semcdb.2016.02.014.CrossRefPubMedGoogle Scholar
  47. 47.
    Kunogi M, Kurihara M, Ikegami TS, Kobayashi T, Shindo N, Kumasaka T, et al. Clinical and genetic spectrum of Birt-Hogg-Dube syndrome patients in whom pneumothorax and/or multiple lung cysts are the presenting feature. J Med Genet. 2010;47(4):281–7.  https://doi.org/10.1136/jmg.2009.070565.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Schmidt LS, Nickerson ML, Warren MB, Glenn GM, Toro JR, Merino MJ, et al. Germline BHD-mutation spectrum and phenotype analysis of a large cohort of families with Birt-Hogg-Dube syndrome. Am J Hum Genet. 2005;76(6):1023–33.  https://doi.org/10.1086/430842.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Hunninghake GW, Costabel U, Ando M, Baughman R, Cordier JF, du Bois R, et al. ATS/ERS/WASOG statement on sarcoidosis. American Thoracic Society/European Respiratory Society/World Association of Sarcoidosis and other Granulomatous Disorders. Sarcoidosis Vasc Diffuse Lung Dis. 1999;16(2):149–73.PubMedGoogle Scholar
  50. 50.
    Baughman RP, Teirstein AS, Judson MA, Rossman MD, Yeager H Jr, Bresnitz EA, et al. Clinical characteristics of patients in a case control study of sarcoidosis. Am J Respir Crit Care Med. 2001;164(10 Pt 1):1885–9.CrossRefGoogle Scholar
  51. 51.
    Iannuzzi MC, Fontana JR. Sarcoidosis: clinical presentation, immunopathogenesis, and therapeutics. JAMA. 2011;305(4):391–9.  https://doi.org/10.1001/jama.2011.10.CrossRefPubMedGoogle Scholar
  52. 52.
    von Bartheld MB, Dekkers OM, Szlubowski A, Eberhardt R, Herth FJ, in’t Veen JC, et al. Endosonography vs conventional bronchoscopy for the diagnosis of sarcoidosis: the GRANULOMA randomized clinical trial. JAMA. 2013;309(23):2457–64.  https://doi.org/10.1001/jama.2013.5823.CrossRefGoogle Scholar
  53. 53.
    Grunewald J, Eklund A. Lofgren’s syndrome: human leukocyte antigen strongly influences the disease course. Am J Respir Crit Care Med. 2009;179(4):307–12.  https://doi.org/10.1164/rccm.200807-1082OC.CrossRefPubMedGoogle Scholar
  54. 54.
    Rossman MD, Thompson B, Frederick M, Maliarik M, Iannuzzi MC, Rybicki BA, et al. HLA-DRB1*1101: a significant risk factor for sarcoidosis in blacks and whites. Am J Hum Genet. 2003;73(4):720–35.  https://doi.org/10.1086/378097.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Suzuki H, Ota M, Meguro A, Katsuyama Y, Kawagoe T, Ishihara M, et al. Genetic characterization and susceptibility for sarcoidosis in Japanese patients: risk factors of BTNL2 gene polymorphisms and HLA class II alleles. Invest Ophthalmol Vis Sci. 2012;53(11):7109–15.  https://doi.org/10.1167/iovs.12-10491.CrossRefPubMedGoogle Scholar
  56. 56.
    Valentonyte R, Hampe J, Huse K, Rosenstiel P, Albrecht M, Stenzel A, et al. Sarcoidosis is associated with a truncating splice site mutation in BTNL2. Nat Genet. 2005;37(4):357–64.  https://doi.org/10.1038/ng1519.CrossRefPubMedGoogle Scholar
  57. 57.
    Li Y, Wollnik B, Pabst S, Lennarz M, Rohmann E, Gillissen A, et al. BTNL2 gene variant and sarcoidosis. Thorax. 2006;61(3):273–4.  https://doi.org/10.1136/thx.2005.056564.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Hofmann S, Franke A, Fischer A, Jacobs G, Nothnagel M, Gaede KI, et al. Genome-wide association study identifies ANXA11 as a new susceptibility locus for sarcoidosis. Nat Genet. 2008;40(9):1103–6.  https://doi.org/10.1038/ng.198.CrossRefPubMedGoogle Scholar
  59. 59.
    Feng X, Zang S, Yang Y, Zhao S, Li Y, Gao X, et al. Annexin A11 (ANXA11) gene polymorphisms are associated with sarcoidosis in a Han Chinese population: a case-control study. BMJ Open. 2014;4(7):e004466.  https://doi.org/10.1136/bmjopen-2013-004466.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Miceli-Richard C, Lesage S, Rybojad M, Prieur AM, Manouvrier-Hanu S, Hafner R, et al. CARD15 mutations in Blau syndrome. Nat Genet. 2001;29(1):19–20.  https://doi.org/10.1038/ng720.CrossRefPubMedGoogle Scholar
  61. 61.
    Sato H, Williams HR, Spagnolo P, Abdallah A, Ahmad T, Orchard TR, et al. CARD15/NOD2 polymorphisms are associated with severe pulmonary sarcoidosis. Eur Respir J. 2010;35(2):324–30.  https://doi.org/10.1183/09031936.00010209.CrossRefPubMedGoogle Scholar
  62. 62.
    Stanley E, Lieschke GJ, Grail D, Metcalf D, Hodgson G, Gall JA, et al. Granulocyte/macrophage colony-stimulating factor-deficient mice show no major perturbation of hematopoiesis but develop a characteristic pulmonary pathology. Proc Natl Acad Sci U S A. 1994;91(12):5592–6.CrossRefGoogle Scholar
  63. 63.
    Whitsett JA, Wert SE, Weaver TE. Diseases of pulmonary surfactant homeostasis. Annu Rev Pathol. 2015;10:371–93.  https://doi.org/10.1146/annurev-pathol-012513-104644.CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Kitamura T, Tanaka N, Watanabe J, Uchida, Kanegasaki S, Yamada Y, et al. Idiopathic pulmonary alveolar proteinosis as an autoimmune disease with neutralizing antibody against granulocyte/macrophage colony-stimulating factor. J Exp Med. 1999;190(6):875–80.CrossRefGoogle Scholar
  65. 65.
    Suzuki T, Sakagami T, Rubin BK, Nogee LM, Wood RE, Zimmerman SL, et al. Familial pulmonary alveolar proteinosis caused by mutations in CSF2RA. J Exp Med. 2008;205(12):2703–10.  https://doi.org/10.1084/jem.20080990.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Tanaka T, Motoi N, Tsuchihashi Y, Tazawa R, Kaneko C, Nei T, et al. Adult-onset hereditary pulmonary alveolar proteinosis caused by a single-base deletion in CSF2RB. J Med Genet. 2011;48(3):205–9.  https://doi.org/10.1136/jmg.2010.082586.CrossRefPubMedGoogle Scholar
  67. 67.
    Seymour JF, Presneill JJ. Pulmonary alveolar proteinosis: progress in the first 44 years. Am J Respir Crit Care Med. 2002;166(2):215–35.  https://doi.org/10.1164/rccm.2109105.CrossRefPubMedGoogle Scholar
  68. 68.
    Borie R, Danel C, Debray MP, Taille C, Dombret MC, Aubier M, et al. Pulmonary alveolar proteinosis. Eur Respir Rev. 2011;20(120):98–107.  https://doi.org/10.1183/09059180.00001311.CrossRefPubMedGoogle Scholar
  69. 69.
    Inoue Y, Trapnell BC, Tazawa R, Arai T, Takada T, Hizawa N, et al. Characteristics of a large cohort of patients with autoimmune pulmonary alveolar proteinosis in Japan. Am J Respir Crit Care Med. 2008;177(7):752–62.  https://doi.org/10.1164/rccm.200708-1271OC.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Amital A, Dux S, Shitrit D, Shpilberg O, Kramer MR. Therapeutic effectiveness of rituximab in a patient with unresponsive autoimmune pulmonary alveolar proteinosis. Thorax. 2010;65(11):1025–6.  https://doi.org/10.1136/thx.2010.140673.CrossRefPubMedGoogle Scholar
  71. 71.
    Ferreira Francisco FA, Pereira e Silva JL, Hochhegger B, Zanetti G, Marchiori E. Pulmonary alveolar microlithiasis. State-of-the-art review. Respir Med. 2013;107(1):1–9.  https://doi.org/10.1016/j.rmed.2012.10.014.CrossRefPubMedGoogle Scholar
  72. 72.
    Harbitz F. Extensive calcification of the lungs as a distinct disease. Arch Intern Med. 1918;21:139–46.CrossRefGoogle Scholar
  73. 73.
    Puhr L. Mikrolithiasis alveolaris pulmonum. Virchows Arch. 1933;290:156–60.CrossRefGoogle Scholar
  74. 74.
    Castellana G, Castellana G, Gentile M, Castellana R, Resta O. Pulmonary alveolar microlithiasis: review of the 1022 cases reported worldwide. Eur Respir Rev. 2015;24(138):607–20.  https://doi.org/10.1183/16000617.0036-2015.CrossRefPubMedGoogle Scholar
  75. 75.
    Corut A, Senyigit A, Ugur SA, Altin S, Ozcelik U, Calisir H, et al. Mutations in SLC34A2 cause pulmonary alveolar microlithiasis and are possibly associated with testicular microlithiasis. Am J Hum Genet. 2006;79(4):650–6.  https://doi.org/10.1086/508263.CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Huqun, Izumi S, Miyazawa H, Ishii K, Uchiyama B, Ishida T, et al. Mutations in the SLC34A2 gene are associated with pulmonary alveolar microlithiasis. Am J Respir Crit Care Med. 2007;175(3):263–8.  https://doi.org/10.1164/rccm.200609-1274OC.CrossRefPubMedGoogle Scholar
  77. 77.
    Poelma DL, Ju MR, Bakker SC, Zimmermann LJ, Lachmann BF, van Iwaarden JF. A common pathway for the uptake of surfactant lipids by alveolar cells. Am J Respir Cell Mol Biol. 2004;30(5):751–8.  https://doi.org/10.1165/rcmb.2003-0127OC.CrossRefPubMedGoogle Scholar
  78. 78.
    Dogan OT, Ozsahin SL, Gul E, Arslan S, Koksal B, Berk S, Ozdemir O, Akkurt I. A frame-shift mutation in the SLC34A2 gene in three patients with pulmonary alveolar microlithiasis in an inbred family. Intern Med. 2010;49(1):45–9.CrossRefGoogle Scholar
  79. 79.
    Ishihara Y, Hagiwara K, Zen K, Huqun HY, Natsuhara A. A case of pulmonary alveolar microlithiasis with an intragenetic deletion in SLC34A2 detected by a genome-wide SNP study. Thorax. 2009;64(4):365–7.CrossRefGoogle Scholar
  80. 80.
    Vismara MF, Colao E, Fabiani F, Bombardiere F, Tamburrini O, Alessio C, Manti F, Pelaia G, Romeo P, Iuliano R, Perrotti N. The sodium-phosphate co-transporter SLC34A2, and pulmonary alveolar microlithiasis: Presentation of an inbred family and a novel truncating mutation in exon 3. Respir Med Case Rep. 2015;16:77–80.PubMedPubMedCentralGoogle Scholar
  81. 81.
    Özbudak IH, Başsorgun CI, Ozbılım G, Lülecı G, Sarper A, Erdoğan A, Taylan F, Altiok E. Pulmonary alveolar microlithiasis with homozygous c.316G > C (p.G106R) mutation: a case report. Turk Patoloji Derg. 2012;28(3):282–5.  https://doi.org/10.5146/tjpath.2012.01138. https://www.ncbi.nlm.nih.gov/pubmed/23011834 CrossRefPubMedGoogle Scholar
  82. 82.
    Ma T, Ren J, Yin J, Ma Z. A pedigree with pulmonary alveolar microlithiasis: a clinical case report and literature review. Cell Biochem Biophys. 2014;70(1):565–72.CrossRefGoogle Scholar
  83. 83.
    Wang H, Yin X, Wu D, Jiang X. SLC34A2 gene compound heterozygous mutation identification in a patient with pulmonary alveolar microlithiasis and computational 3D protein structure prediction. Meta Gene. 2014;2:557–64.CrossRefGoogle Scholar
  84. 84.
    Izumi H, Kurai J, Kodani M, Watanabe M, Yamamoto A, Nanba E, Adachi K, Igishi T, Shimizu E. A novel SLC34A2 mutation in a patient with pulmonary alveolar microlithiasis. Hum Genome Var. 2017 Jan 26;4:16047.CrossRefGoogle Scholar
  85. 85.
    Jönsson ÅL, Hilberg O, Bendstrup EM, Mogensen S, Simonsen U. SLC34A2 gene mutation may explain comorbidity of pulmonary alveolar microlithiasis and aortic valve sclerosis. Am J Respir Crit Care Med. 2012;185(4):464.CrossRefGoogle Scholar
  86. 86.
    Proesmans M, Boon M, Verbeken E, Ozcelik U, Kiper N, Van de Casseye W, De Boeck K. Pulmonary alveolar microlithiasis: a case report and review of the literature. Eur J Pediatr. 2012;171(7):1069–72.CrossRefGoogle Scholar
  87. 87.
    Mariotta S, Ricci A, Papale M, De Clementi F, Sposato B, Guidi L, et al. Pulmonary alveolar microlithiasis: report on 576 cases published in the literature. Sarcoidosis Vasc Diffuse Lung Dis. 2004;21(3):173–81.PubMedGoogle Scholar
  88. 88.
    Stamatis G, Zerkowski HR, Doetsch N, Greschuchna D, Konietzko N, Reidemeister JC. Sequential bilateral lung transplantation for pulmonary alveolar microlithiasis. Ann Thorac Surg. 1993;56(4):972–5.CrossRefGoogle Scholar
  89. 89.
    Edelman JD, Bavaria J, Kaiser LR, Litzky LA, Palevsky HI, Kotloff RM. Bilateral sequential lung transplantation for pulmonary alveolar microlithiasis. Chest. 1997;112(4):1140–4.CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Haruhiko Furusawa
    • 1
  • Masahiro Masuo
    • 1
  • Yoshihisa Nukui
    • 1
  • Yasunari Miyazaki
    • 2
    • 1
  • Naohiko Inase
    • 1
  1. 1.Department of Respiratory Medicine, Graduate School of Medical and Dental SciencesTMDUTokyoJapan
  2. 2.Student Support and Health Administration OrganizationTokyo Medical and Dental University (TMDU)TokyoJapan

Personalised recommendations