Skip to main content
SpringerLink
Log in

Pulmonary Alveolar Microlithiasis

  • Chapter
  • First Online:
Molecular Basis of Pulmonary Disease

Part of the book series: Respiratory Medicine ((RM))

Abstract

Pulmonary alveolar microlithiasis (PAM: OMIM265100) is an autosomal recessive disorder characterized by the intra-alveolar formation of microliths that are mainly composed of calcium phosphate. Microliths are found in about 80% of the alveoli. They grow very slowly and finally occupy most of the alveolar space. Mild-to-moderate chronic inflammation and fibrosis are observed mainly in the interstitium asymptomatic diagnosed of their diseases in their childhood where the disease is often discovered incidentally on a chest xray taken for a different purpose. The disease usually takes a chronic, slowly progressive course. Patients are generally free of symptoms until middle age, when respiratory insufficiency gradually develops. Many patients die of respiratory failure. In 2006, two independent researchers reported that homozygous loss-of-function mutations in the SLC34A2 gene is present in PAM patients. SLC34A2 encodes a type IIb sodium-dependent phosphate transporter that is expressed in type II alveolar cells. Loss of phosphate transporter function in alveolar type II cells is considered to be the cause of PAM.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Harbitz F. Extensive calcification of the lungs as a distinct disease. Arch Int Med 1918;21:139–46.

    Google Scholar 

  2. Puhr L. Mikrolithiasis alveolaris pulmonum. Virchows Arch Pathol Anat 1933;290:156–60.

    Article  Google Scholar 

  3. Ucan ES, Keyf AI, Aydilek R, Yalcin Z, Sebit S, Kudu M, et al. Pulmonary alveolar microlithiasis: Review of Turkish reports. Thorax 1993;48:171–3.

    Article  CAS  PubMed  Google Scholar 

  4. Mariotta S, Guidi L, Papale M, Ricci A, Bisetti A. Pulmonary alveolar microlithiasis: review of Italian reports. Eur J Epidemiol 1997;13:587–90.

    Article  CAS  PubMed  Google Scholar 

  5. Castellana G, Gentile M, Castellana R, Fiorente P, Lamorgese V. Pulmonary alveolar microlithiasis: Clinical features, evolution of the phenotype, and review of the literature. Am J Med Genet 2002;111:220–4.

    Article  CAS  PubMed  Google Scholar 

  6. 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;21:173–81.

    PubMed  Google Scholar 

  7. Hagiwara K, Huqun IS, Miyazawa H, Uchiyama B, Ishida T, et al. The autozygous segments predicted by a genome-wide SNP typing revealed mutations in the type IIb sodium phosphate co-transporter (SLC34A2) causing pulmonary alveolar microlithiasis. Proc Am Thorac Soc 2006;3:A102.

    Google Scholar 

  8. Huqun IS, 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;175:263–8.

    Article  CAS  PubMed  Google Scholar 

  9. 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;79:650–6.

    Article  CAS  PubMed  Google Scholar 

  10. Senyigit A, Yaramis A, Gurkan F, Kirbas G, Buyukbayram H, Nazaroglu H, et al. Pulmonary alveolar microlithiasis: A rare familial inheritance with report of six cases in a family. Contribution of six new cases to the number of case reports in Turkey. Respiration 2001;68:204–9.

    Article  CAS  PubMed  Google Scholar 

  11. Chan ED, Morales DV, Welsh CH, McDermott MT, Schwarz MI. Calcium deposition with or without bone formation in the lung. Am J Respir Crit Care Med 2002;165:1654–69.

    Article  PubMed  Google Scholar 

  12. Takahashi H, Chiba H, Shiratori M, Tachibana T, Abe S. Elevated serum surfactant protein A and D in pulmonary alveolar microlithiasis. Respirology 2006;11:330–3.

    Article  PubMed  Google Scholar 

  13. Schmidt H, Lörcher U, Kitz R, Zielen S, Ahrens P, König R. Pulmonary alveolar microlithiasis in children. Pediatr Radiol 1996;26:33–6.

    Article  CAS  PubMed  Google Scholar 

  14. Palombini BC, Porto NS, Wallau CU, Camargo JJ. Bronchopulmonary lavage in alveolar microlithiasis. Chest 1981;80:242–3.

    Article  CAS  PubMed  Google Scholar 

  15. Ishida T, Furutani M. Ultrastructural observation of bronchoalveolar lavage fluid in pulmonary alveolar microlithiasis. J Clin Electron Microscopy 1992;25:55–61.

    Google Scholar 

  16. Fraser RS, Müller NL, Colman N, Paré PD (eds.). Pulmonary alveolar microlithiasis. Diagnosis of Diseases of the Chest. Vol. IV, WB Saundres, Philadelphia, 4th Ed. 1999; 2719–23.

    Google Scholar 

  17. Sosman MC, Dodd GD, Jones WD, Pillmore GU. The familial occurrence of pulmonary alveolar microlithiasis. Am J Roentgenol Radium Ther Nucl Med 1957;77:947–1012.

    CAS  PubMed  Google Scholar 

  18. Helbich TH, Wojnarovsky C, Wunderbaldinger P, Heinz-Peer G, Eichler I, Herold CJ. Pulmonary alveolar microlithiasis in children: Radiographic and high-resolution CT findings. Am J Roentgenol 1997;168:63–5.

    CAS  Google Scholar 

  19. Winzelberg GG, Boller M, Sachs M, Weinberg J. CT evaluation of pulmonary alveolar microlithiasis. J Comput Assist Tomogr 1984;8:1029–31.

    Article  CAS  PubMed  Google Scholar 

  20. Chalmers AG, Wyatt J, Robinson PJ. Computed tomographic and pathological findings in pulmonary alveolar microlithiasis. Brit J Radiol 1986;59:408–11.

    Article  CAS  PubMed  Google Scholar 

  21. Cluzel P, Grenier P, Bernadac P, Laurent F, Picard JD. Pulmonary alveolar microlithiasis: CT findings. J Comput Assist Tomogr 1991;15:938–42.

    Article  CAS  PubMed  Google Scholar 

  22. Korn MA, Schurawitzki H, Klepetko W, Burghuber OC. Pulmonary alveolar microlithiasis: Findings on high-resolution CT. Am J Roentgenol 1992;158:981–2.

    CAS  Google Scholar 

  23. Miro JM, Moreno A, Coca A, Segura F, Soriano E. Pulmonary alveolar microlithiasis with an unusual radiological pattern. Br J Dis Chest 1982;76:91–6.

    Article  CAS  PubMed  Google Scholar 

  24. Melamed JW, Sostman HD, Ravin CE. Interstitial thickening in pulmonary alveolar microlithiasis: An underappreciated finding. J Thorac Imaging 1994;9:126–8.

    Article  CAS  PubMed  Google Scholar 

  25. Sumikawa H, Johkoh T, Tomiyama N, Hamada S, Koyama M, Tsubamoto M, et al. Pulmonary alveolar microlithiasis: CT and pathologic findings in 10 patients. Monaldi Arch Chest Dis 2005;63:59–64.

    CAS  PubMed  Google Scholar 

  26. Brown ML, Swee RG, Olson RJ, Bender CE. Pulmonary uptake of 99mTc diphosphonate in alveolar microlithiasis. Am J Roentgenol 1978;131:703–4.

    CAS  Google Scholar 

  27. Shigeno C, Fukunaga M, Morita R, Maeda H, Hino M, Torizuka K. Bone scintigraphy in pulmonary alveolar microlithiasis: A comparative study of radioactivity and density distribution. Clin Nuclear Med 1982;7:103–7.

    Article  CAS  Google Scholar 

  28. Prakash UBS, Barham SS, Rosenow EC III, Brown ML, Payne WS. Pulmonary alveolar microlithiasis. A review including ultrastructural and pulmonary function studies. Mayo Clin Proc 1983;58:290–300.

    CAS  PubMed  Google Scholar 

  29. Moran CA, Hochholzer L, Hasleton PS, Johnson FB, Koss MN. Pulmonary alveolar microlithiasis. A clinicopathologic and chemical analysis of seven cases. Arch Pathol Lab Med 1997;121:607–11.

    CAS  PubMed  Google Scholar 

  30. Prakash UBS. Pulmonary alveolar microlithiasis. Semin Respir Crit Care Med 2002;23:103–13.

    Article  PubMed  Google Scholar 

  31. Ishii N, Ueda S, Hayashi S, Matsumoto S, Hayashida F, Tsukune U, et al. Ultrastructural study of the pulmonary alveolar microlithiasis-with special reference of the scanning and transmission electronmicroscopic findings. J Clin Electron Microscopy 1976;9:437–8.

    Google Scholar 

  32. Kawakami M, Sato S, Takishima T. Electro microscopic studies on pulmonary alveolar microlithiasis. Tohoku J Exp Med 1978;126:343–61.

    Article  CAS  PubMed  Google Scholar 

  33. Kanat F, Teke T, Imecik O. Pulmonary alveolar microlithiasis with epididymal and periurethral calcifications causing obstructive azospermia. Int J Tuberc Lung Dis 2004;8:1275.

    CAS  PubMed  Google Scholar 

  34. Mascie-Taylor BH, Wardman AG, Madden CA, Page RL. A case of alveolar microlithiasis: Observation over 22 years and recovery of material by lavage. Thorax 1985;40:952–3.

    Article  CAS  PubMed  Google Scholar 

  35. O’Neill RP, Cohn JE, Pellegrino ED. Pulmonary alveolar microlithiasis-a family study. Ann Intern Med 1967;67:957–67.

    PubMed  Google Scholar 

  36. Özçelik U, Gülsün M, Göçmen A, Arıyürek M, Kiper N, Anadol D, et al. Treatment and follow-up of pulmonary alveolar microlithiasis with disodium editronate: Radiological demonstration. Pediatr Radiol 2002;32:380–3.

    Article  PubMed  Google Scholar 

  37. Stamatis G, Zerkowski HR, Doetsch N, Greschuchna D, Konietzko N, Reidemeister JC. Sequential bilateral lung transplantation for pulmonary alveolar microlithiasis. Ann Thorac Surg 1993;56:972–5.

    Article  CAS  PubMed  Google Scholar 

  38. Edelman JD, Bavaria J, Kaiser LR, Litzky LA, Palevsky HI, Kotloff RM. Bilateral sequential lung transplantation for pulmonary alveolar microlithiasis. Chest 1997;112:1140–4.

    Article  CAS  PubMed  Google Scholar 

  39. Bonnette P, Bisson, Ben El Kadi N, Colchen A, Leroy M, Fischler M, et al. Bilateral single lung transplantation. Complications and results in 14 patients. Eur J Cardiothorac Surg 1992;6:550–4.

    Article  CAS  PubMed  Google Scholar 

  40. Jackson KB, Modry DL, Halenar J, L’abbe J, Winton TL, Lien DC. Single lung transplantation for pulmonary alveolar microlithiasis. J Heart Lung Transplant 2001;20:226.

    Article  PubMed  Google Scholar 

  41. Xu H, Bai L, Collins JF, Ghishan FK. Molecular cloning, functional characterization, tissue distribution, and chromosomal localization of a human, small intestinal sodium-phosphate (Na+-Pi) transporter (SLC34A2). Genomics 1999;62:281–4.

    Article  CAS  PubMed  Google Scholar 

  42. Feild JA, Zhang L, Brun KA, Brooks DP, Edwards RM. Cloning and functional characterization of a sodium-dependent phosphate transporter expressed in human lung and small intestine. Biochem Biophys Res Comm 1999;258:578–82.

    Article  CAS  PubMed  Google Scholar 

  43. Lander ES, Botstein D. Homozygosity mapping: A way to map human recessive traits with the DNA of inbread children. Science 1987;236:1567–70.

    Article  CAS  PubMed  Google Scholar 

  44. Clark AG. The size distribution of homozygous segments in the human genome. Am J Hum Genet 1999;65:1489–92.

    Article  CAS  PubMed  Google Scholar 

  45. Prié D, Huart V, Bakouh N, Planelles G, Dellis O, Gérard B, et al. Nephrolithiasis and osteoporosis associated with hypophosphatemia caused by mutations in the type 2a sodium-phosphate cotransporter. N Engl J Med 2002;347:983–91.

    Article  PubMed  Google Scholar 

  46. Bergwitz C, Roslin NM, Tieder M, Loredo-Osti JC, Bastepe M, Abu-Zahra H, et al. SLC34A3 mutations in patients with hereditary hypophosphatemic rickets with hypercalciuria predict a key role for the sodium-phosphate cotransporter NaPi-IIc in maintaining phosphate homeostasis. Am J Hum Genet 2006;78:179–92.

    Article  CAS  PubMed  Google Scholar 

  47. Murer H, Forster I, Biber J. The sodium phosphate cotransporter family SLC34. Euro J Physiol 2004;447:763–7.

    Article  CAS  Google Scholar 

  48. Imaizumi Y. A recent survey of consanguineous marriages in Japan. Clin Genet 1986;30:230–3.

    Article  CAS  PubMed  Google Scholar 

  49. Al-Awadi SA, Moussa MA, Naguib KK, Farag TI, Teebi AS el-Khalifa M, et al. Consanguinity among the Kuwaiti population. Clin Genet 1985;27:483–6.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Respiratory Medicine, Saitama Medical School, Saitama, Japan

    Koichi Hagiwara MD

  2. Department of Radiology, Osaka University Hospital, Osaka, Japan

    Takeshi Johkoh MD

  3. Department of Internal Medicine, Aizenbashi Hospital, Osaka, Japan

    Teruo Tachibana MD

Authors
  1. Koichi Hagiwara MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Takeshi Johkoh MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Teruo Tachibana MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Div. Pulmonary & Critical Care, University of Cincinnati, Albert Sabin Way 231, Cincinnati, 45267, USA

    Francis X. McCormack

  2. Div. Pulmonary & Critical Care, University of Cincinnati, Albert Sabin Way 231, Cincinnati, 45267, USA

    Ralph J. Panos

  3. Medical Center, Cincinnati Children's Hospital, Burnet Ave. 3333, Cincinnati, 45229, USA

    Bruce C. Trapnell

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Hagiwara, K., Johkoh, T., Tachibana, T. (2010). Pulmonary Alveolar Microlithiasis. In: McCormack, F., Panos, R., Trapnell, B. (eds) Molecular Basis of Pulmonary Disease. Respiratory Medicine. Humana Press. https://doi.org/10.1007/978-1-59745-384-4_15

Download citation

  • DOI: https://doi.org/10.1007/978-1-59745-384-4_15

  • Published:

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-963-5

  • Online ISBN: 978-1-59745-384-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation