Pulmonary Alveolar Microlithiasis

  • Koichi Hagiwara
  • Takeshi Johkoh
  • Teruo Tachibana
Part of the Respiratory Medicine book series (RM)


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.


diffuse pulmonary shadow phosphorus transporter intra-alveolar microliths autosomal recessive inheritance 


  1. 1.
    Harbitz F. Extensive calcification of the lungs as a distinct disease. Arch Int Med 1918;21:139–46.Google Scholar
  2. 2.
    Puhr L. Mikrolithiasis alveolaris pulmonum. Virchows Arch Pathol Anat 1933;290:156–60.CrossRefGoogle Scholar
  3. 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.CrossRefPubMedGoogle Scholar
  4. 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.CrossRefPubMedGoogle Scholar
  5. 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.CrossRefPubMedGoogle Scholar
  6. 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.PubMedGoogle Scholar
  7. 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. 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.CrossRefPubMedGoogle Scholar
  9. 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.CrossRefPubMedGoogle Scholar
  10. 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.CrossRefPubMedGoogle Scholar
  11. 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.CrossRefPubMedGoogle Scholar
  12. 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.CrossRefPubMedGoogle Scholar
  13. 13.
    Schmidt H, Lörcher U, Kitz R, Zielen S, Ahrens P, König R. Pulmonary alveolar microlithiasis in children. Pediatr Radiol 1996;26:33–6.CrossRefPubMedGoogle Scholar
  14. 14.
    Palombini BC, Porto NS, Wallau CU, Camargo JJ. Bronchopulmonary lavage in alveolar microlithiasis. Chest 1981;80:242–3.CrossRefPubMedGoogle Scholar
  15. 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. 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. 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.PubMedGoogle Scholar
  18. 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.Google Scholar
  19. 19.
    Winzelberg GG, Boller M, Sachs M, Weinberg J. CT evaluation of pulmonary alveolar microlithiasis. J Comput Assist Tomogr 1984;8:1029–31.CrossRefPubMedGoogle Scholar
  20. 20.
    Chalmers AG, Wyatt J, Robinson PJ. Computed tomographic and pathological findings in pulmonary alveolar microlithiasis. Brit J Radiol 1986;59:408–11.CrossRefPubMedGoogle Scholar
  21. 21.
    Cluzel P, Grenier P, Bernadac P, Laurent F, Picard JD. Pulmonary alveolar microlithiasis: CT findings. J Comput Assist Tomogr 1991;15:938–42.CrossRefPubMedGoogle Scholar
  22. 22.
    Korn MA, Schurawitzki H, Klepetko W, Burghuber OC. Pulmonary alveolar microlithiasis: Findings on high-resolution CT. Am J Roentgenol 1992;158:981–2.Google Scholar
  23. 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.CrossRefPubMedGoogle Scholar
  24. 24.
    Melamed JW, Sostman HD, Ravin CE. Interstitial thickening in pulmonary alveolar microlithiasis: An underappreciated finding. J Thorac Imaging 1994;9:126–8.CrossRefPubMedGoogle Scholar
  25. 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.PubMedGoogle Scholar
  26. 26.
    Brown ML, Swee RG, Olson RJ, Bender CE. Pulmonary uptake of 99mTc diphosphonate in alveolar microlithiasis. Am J Roentgenol 1978;131:703–4.Google Scholar
  27. 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.CrossRefGoogle Scholar
  28. 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.PubMedGoogle Scholar
  29. 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.PubMedGoogle Scholar
  30. 30.
    Prakash UBS. Pulmonary alveolar microlithiasis. Semin Respir Crit Care Med 2002;23:103–13.CrossRefPubMedGoogle Scholar
  31. 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. 32.
    Kawakami M, Sato S, Takishima T. Electro microscopic studies on pulmonary alveolar microlithiasis. Tohoku J Exp Med 1978;126:343–61.CrossRefPubMedGoogle Scholar
  33. 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.PubMedGoogle Scholar
  34. 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.CrossRefPubMedGoogle Scholar
  35. 35.
    O’Neill RP, Cohn JE, Pellegrino ED. Pulmonary alveolar microlithiasis-a family study. Ann Intern Med 1967;67:957–67.PubMedGoogle Scholar
  36. 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.CrossRefPubMedGoogle Scholar
  37. 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.CrossRefPubMedGoogle Scholar
  38. 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.CrossRefPubMedGoogle Scholar
  39. 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.CrossRefPubMedGoogle Scholar
  40. 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.CrossRefPubMedGoogle Scholar
  41. 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.CrossRefPubMedGoogle Scholar
  42. 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.CrossRefPubMedGoogle Scholar
  43. 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.CrossRefPubMedGoogle Scholar
  44. 44.
    Clark AG. The size distribution of homozygous segments in the human genome. Am J Hum Genet 1999;65:1489–92.CrossRefPubMedGoogle Scholar
  45. 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.CrossRefPubMedGoogle Scholar
  46. 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.CrossRefPubMedGoogle Scholar
  47. 47.
    Murer H, Forster I, Biber J. The sodium phosphate cotransporter family SLC34. Euro J Physiol 2004;447:763–7.CrossRefGoogle Scholar
  48. 48.
    Imaizumi Y. A recent survey of consanguineous marriages in Japan. Clin Genet 1986;30:230–3.CrossRefPubMedGoogle Scholar
  49. 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.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Koichi Hagiwara
    • 1
  • Takeshi Johkoh
    • 2
  • Teruo Tachibana
    • 3
  1. 1.Department of Respiratory MedicineSaitama Medical SchoolSaitamaJapan
  2. 2.Department of RadiologyOsaka University HospitalOsakaJapan
  3. 3.Department of Internal MedicineAizenbashi HospitalOsakaJapan

Personalised recommendations