Download PDF
Semin Respir Crit Care Med 2020; 41(02): 280-287
DOI: 10.1055/s-0040-1702211
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Pulmonary Alveolar Microlithiasis

Brian M. Shaw
1   Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio
,
Steven D. Shaw
1   Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio
,
Francis X. McCormack
1   Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio
2   Division of Pulmonary, Critical Care, and Sleep Medicine, University of Cincinnati, Cincinnati, Ohio
› Author Affiliations
Further Information

Publication History

Publication Date:
12 April 2020 (online)

    Permissions and Reprints

Abstract

Pulmonary alveolar microlithiasis (PAM) is a rare, autosomal recessive disorder that is caused by mutations in SCL34A2 that encodes for the type IIb sodium-dependent phosphate cotransporter (Npt2b). The loss of Npt2b transporter function from alveolar epithelial cells results in failure to export inorganic phosphate from the alveolar lining fluid, which then accumulates, binds to calcium, and forms hydroxyapatite microliths. Radiographs and computed tomography of the chest demonstrate hyperdense infiltrates that are often quite dramatic and distinctive, and in many cases, the diagnosis can be made without invasive measures. The most common presenting symptom of PAM is dyspnea on exertion, but the disease is frequently first noted as an incidental finding in asymptomatic patients who have chest films performed for unrelated reasons. Pulmonary fibrosis, pulmonary hypertension, and respiratory failure can develop as the disease progresses, and treatment remains supportive. Lung transplantation is an option for those with end stage disease.

Keywords

pulmonary alveolar microlithiasis - pulmonary ossification - pulmonary calcification - type IIb sodium-dependent phosphate cotransporter - Npt2b - NaPi-2b - SCL34A2
 

  • References

  • 1 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) 607-620
    CrossrefPubMedGoogle Scholar
  • 2 Saito A, McCormack FX. Pulmonary alveolar microlithiasis. Clin Chest Med 2016; 37 (03) 441-448
    PubMedGoogle Scholar
  • 3 Kashyap S, Mohapatra PR. Pulmonary alveolar microlithiasis. Lung India 2013; 30 (02) 143-147
    CrossrefPubMedGoogle Scholar
  • 4 Huqun, Izumi S, Miyazawa H. , et al. Mutations in the SLC34A2 gene are associated with pulmonary alveolar microlithiasis. Am J Respir Crit Care Med 2007; 175 (03) 263-268
    CrossrefPubMedGoogle Scholar
  • 5 Corut A, Senyigit A, Ugur SA. , et al. Mutations in SLC34A2 cause pulmonary alveolar microlithiasis and are possibly associated with testicular microlithiasis. Am J Hum Genet 2006; 79 (04) 650-656
    CrossrefPubMedGoogle Scholar
  • 6 Sosman MC, Dodd GD, Jones WD, Pillmore GU. The familial occurrence of pulmonary alveolar microlithiasis. Am J Roentgenol Radium Ther Nucl Med 1957; 77 (06) 947-1012
    PubMedGoogle Scholar
  • 7 Mariotta S, Ricci A, Papale M. , et al. Pulmonary alveolar microlithiasis: report on 576 cases published in the literature. Sarcoidosis Vasc Diffuse Lung Dis 2004; 21 (03) 173-181
    PubMedGoogle Scholar
  • 8 Caffrey PR, Altman RS. Pulmonary alveolar microlitbiasis occurring in premature twins. J Pediatr 1965; 66: 758-763
    CrossrefPubMedGoogle Scholar
  • 9 Krishnakurup J, Abdelsayed G. The calcareous lung. Mayo Clin Proc 2011; 86 (02) 85
    CrossrefPubMedGoogle Scholar
  • 10 Pulmonary Alveolar Microlithiasis. 2019 . Available at: https://ghr.nlm.nih.gov/condition/pulmonary-alveolar-microlithiasis . Accessed August 19, 2019
    PubMedGoogle Scholar
  • 11 SLC34A2 gene, solute carrier family 34, member 2. 2019 Available at: https://ghr.nlm.nih.gov/gene/SLC34A2# . Accessed August 19, 2019
    PubMedGoogle Scholar
  • 12 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 (01) 1-9
    CrossrefPubMedGoogle Scholar
  • 13 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 (01) 565-572
    CrossrefPubMedGoogle Scholar
  • 14 Yang W, Wang Y, Pu Q. , et al. Elevated expression of SLC34A2 inhibits the viability and invasion of A549 cells. Mol Med Rep 2014; 10 (03) 1205-1214
    CrossrefPubMedGoogle Scholar
  • 15 Saito A, Nikolaidis NM, Amlal H. , et al. Modeling pulmonary alveolar microlithiasis by epithelial deletion of the Npt2b sodium phosphate cotransporter reveals putative biomarkers and strategies for treatment. Sci Transl Med 2015; 7 (313) 313ra181
    CrossrefPubMedGoogle Scholar
  • 16 Sabbagh Y, O'Brien SP, Song W. , et al. Intestinal npt2b plays a major role in phosphate absorption and homeostasis. J Am Soc Nephrol 2009; 20 (11) 2348-2358
    CrossrefPubMedGoogle Scholar
  • 17 Schiavi SC, Tang W, Bracken C. , et al. Npt2b deletion attenuates hyperphosphatemia associated with CKD. J Am Soc Nephrol 2012; 23 (10) 1691-1700
    CrossrefPubMedGoogle Scholar
  • 18 Bacconi A, Virkki LV, Biber J, Murer H, Forster IC. Renouncing electroneutrality is not free of charge: switching on electrogenicity in a Na+-coupled phosphate cotransporter. Proc Natl Acad Sci U S A 2005; 102 (35) 12606-12611
    CrossrefPubMedGoogle Scholar
  • 19 Mancusso R, Gregorio GG, Liu Q, Wang DN. Structure and mechanism of a bacterial sodium-dependent dicarboxylate transporter. Nature 2012; 491 (7425): 622-626
    PubMedGoogle Scholar
  • 20 Iyonaga K, Suga M, Yamamoto T, Ichiyasu H, Miyakawa H, Ando M. Elevated bronchoalveolar concentrations of MCP-1 in patients with pulmonary alveolar proteinosis. Eur Respir J 1999; 14 (02) 383-389
    PubMedGoogle Scholar
  • 21 McCormack FX, Whitsett JA. The pulmonary collectins, SP-A and SP-D, orchestrate innate immunity in the lung. J Clin Invest 2002; 109 (06) 707-712
    CrossrefPubMedGoogle Scholar
  • 22 Takahashi H, Chiba H, Shiratori M, Tachibana T, Abe S. Elevated serum surfactant protein A and D in pulmonary alveolar microlithiasis. Respirology 2006; 11 (03) 330-333
    CrossrefPubMedGoogle Scholar
  • 23 Akella A, Deshpande SB. Pulmonary surfactants and their role in pathophysiology of lung disorders. Indian J Exp Biol 2013; 51 (01) 5-22
    PubMedGoogle Scholar
  • 24 McCarthy C, Lee E, Bridges JP. , et al. Statin as a novel pharmacotherapy of pulmonary alveolar proteinosis. Nat Commun 2018; 9 (01) 3127
    CrossrefPubMedGoogle Scholar
  • 25 Sallese A, Suzuki T, McCarthy C. , et al. Targeting cholesterol homeostasis in lung diseases. Sci Rep 2017; 7 (01) 10211
    CrossrefPubMedGoogle Scholar
  • 26 Zhang XD, Gao JM, Luo JM, Zhao Y. Pulmonary alveolar microlithiasis: a case report and review of the literature. Exp Ther Med 2018; 15 (01) 831-837
    PubMedGoogle Scholar
  • 27 Simon C, Lewis T, Neemuchwala F, Arteta M, Rabah R. Pulmonary alveolar microlithiasis: A case report with a novel mutation in the SLC34A2 gene and review of the literature. Human Pathol Case Rep 2018; 13: 33-35
    PubMedGoogle Scholar
  • 28 Pant K, Shah A, Mathur RK, Chhabra SK, Jain SK. Pulmonary alveolar microlithiasis with pleural calcification and nephrolithiasis. Chest 1990; 98 (01) 245-246
    CrossrefPubMedGoogle Scholar
  • 29 Piesiak P, Kasibowska-Kuźniar K, Jankowska R. [Pulmonary alveolar microlithiasis in a patient with urolithiasis and cholelithiasis]. Pneumonol Alergol Pol 2001; 69 (5-6): 285-289
    PubMedGoogle Scholar
  • 30 Coetzee T. Pulmonary alveolar microlithiasis with involvement of the sympathetic nervous system and gonads. Thorax 1970; 25 (05) 637-642
    CrossrefPubMedGoogle Scholar
  • 31 Arslan A, Yalin T, Akan H, Belet U. Pulmonary alveolar microlithiasis associated with calcifications in the seminal vesicles. J Belge Radiol 1996; 79 (03) 118-119
    PubMedGoogle Scholar
  • 32 Kanat F, Teke T, Imecik O. Pulmonary alveolar microlithiasis with epididymal and periurethral calcifications causing obstructive azospermia. Int J Tuberc Lung Dis 2004; 8 (10) 1275
    PubMedGoogle Scholar
  • 33 Jönsson AL, 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 (04) 464
    PubMedGoogle Scholar
  • 34 Kiatboonsri S, Charoenpan P, Vathesatogkit P, Boonpucknavig V. Pulmonary alveolar microlithiasis: report of five cases and literature review. J Med Assoc Thai 1985; 68 (12) 672-677
    PubMedGoogle Scholar
  • 35 Tachibana T, Hagiwara K, Johkoh T. Pulmonary alveolar microlithiasis: review and management. Curr Opin Pulm Med 2009; 15 (05) 486-490
    CrossrefPubMedGoogle Scholar
  • 36 Khaladkar SM, Kondapavuluri SK, Kamal A, Kalra R, Kuber R. Pulmonary alveolar microlithiasis - clinico-radiological dissociation - a case report with Radiological review. J Radiol Case Rep 2016; 10 (01) 14-21
    PubMedGoogle Scholar
  • 37 Francisco FA, Rodrigues RS, Barreto MM. , et al. Can chest high-resolution computed tomography findings diagnose pulmonary alveolar microlithiasis?. Radiol Bras 2015; 48 (04) 205-210
    CrossrefPubMedGoogle Scholar
  • 38 Chalmers AG, Wyatt J, Robinson PJ. Computed tomographic and pathological findings in pulmonary alveolar microlithiasis. Br J Radiol 1986; 59 (700) 408-411
    CrossrefPubMedGoogle Scholar
  • 39 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 (06) 607-611
    PubMedGoogle Scholar
  • 40 Kawakami M, Sato S, Takishima T. Electron microscopic studies on pulmonary alveolar microlithiasis. Tohoku J Exp Med 1978; 126 (04) 343-361
    CrossrefPubMedGoogle Scholar
  • 41 Mahmood K, Ubaid M, Mahmood A. Pulmonary microlithiasis - a case report. Respir Med Case Rep 2016; 19: 112-114
    PubMedGoogle Scholar
  • 42 Arpağ H, Sayan M, Atilla N. , et al. A case of pulmonary alveolar microlithiasis diagnosed by transbronchial biopsy. Turk Thorac J 2017; 18 (04) 134-136
    CrossrefPubMedGoogle Scholar
  • 43 Prakash UB, Barham SS, Rosenow III EC, Brown ML, Payne WS. Pulmonary alveolar microlithiasis. A review including ultrastructural and pulmonary function studies. Mayo Clin Proc 1983; 58 (05) 290-300
    PubMedGoogle Scholar
  • 44 Delic JA, Fuhrman CR, Trejo Bittar HE. Pulmonary alveolar microlithiasis: AIRP best cases in radiologic-pathologic correlation. Radiographics 2016; 36 (05) 1334-1338
    CrossrefPubMedGoogle Scholar
  • 45 Lewinsohn DM, Leonard MK, LoBue PA. , et al. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: diagnosis of tuberculosis in adults and children. Clin Infect Dis 2017; 64 (02) e1-e33
    CrossrefPubMedGoogle Scholar
  • 46 Little BP. Sarcoidosis: overview of pulmonary manifestations and imaging. Semin Roentgenol 2015; 50 (01) 52-64
    CrossrefPubMedGoogle Scholar
  • 47 Mariotta S, Guidi L, Mattia P. , et al. Pulmonary microlithiasis. Report of two cases. Respiration 1997; 64 (02) 165-169
    CrossrefPubMedGoogle Scholar
  • 48 Ozçelik U, Gülsün M, Göçmen A. , et al. Treatment and follow-up of pulmonary alveolar microlithiasis with disodium editronate: radiological demonstration. Pediatr Radiol 2002; 32 (05) 380-383
    CrossrefPubMedGoogle Scholar
  • 49 Ozcelik U, Yalcin E, Ariyurek M. , et al. Long-term results of disodium etidronate treatment in pulmonary alveolar microlithiasis. Pediatr Pulmonol 2010; 45 (05) 514-517
    PubMedGoogle Scholar
  • 50 Jankovic S, Pavlov N, Ivkosic A. , et al. Pulmonary alveolar microlithiasis in childhood: clinical and radiological follow-up. Pediatr Pulmonol 2002; 34 (05) 384-387
    CrossrefPubMedGoogle Scholar
  • 51 Taillé C, Debray MP, Danel C, Serhal A, Pradère P, Crestani B. Calcium-solubilizing sodium thiosulfate failed to improve pulmonary alveolar microlithiasis: Evaluation of calcium content with CT scan. Respir Med Res 2019; 75: 10-12
    PubMedGoogle Scholar
  • 52 Palombini BC, da Silva Porto N, Wallau CU, Camargo JJ. Bronchopulmonary lavage in alveolar microlithiasis. Chest 1981; 80 (02) 242-243
    CrossrefPubMedGoogle Scholar
  • 53 Mariotta S, Onofri A, Bruno P, Ricci A. Pulmonary Alveolar Microlithiasis. In: Cottin V, Cordier J-F, Richeldi L. , eds. Orphan Lung Diseases: A Clinical Guide to Rare Lung Disease. London: Springer London; 2015: 305-313
    CrossrefGoogle Scholar
  • 54 Alrossais NM, Alshammari AM, Alrayes AM. , et al. Pulmonary hypertension and polycythemia secondary to pulmonary alveolar microlithiasis treated with sequential bilateral lung transplant: a case study and literature review. Am J Case Rep 2019; 20: 1114-1119
    CrossrefPubMedGoogle Scholar
  • 55 Vock DM, Durheim MT, Tsuang WM. , et al. Survival benefit of lung transplantation in the modern era of lung allocation. Ann Am Thorac Soc 2017; 14 (02) 172-181
    PubMedGoogle Scholar
  • 56 Jamjoom L, Meziane M, Renapurkar RD. Dendriform pulmonary ossification: Report of two cases. Indian J Radiol Imaging 2013; 23 (01) 15-18
    Article in Thieme ConnectPubMedGoogle Scholar
  • 57 Amin SB, Slater R, Mohammed TL. Pulmonary calcifications: a pictorial review and approach to formulating a differential diagnosis. Curr Probl Diagn Radiol 2015; 44 (03) 267-276
    CrossrefPubMedGoogle Scholar
  • 58 Belém LC, Zanetti G, Souza Jr AS. , et al. Metastatic pulmonary calcification: state-of-the-art review focused on imaging findings. Respir Med 2014; 108 (05) 668-676
    CrossrefPubMedGoogle Scholar
  • 59 Bendayan D, Barziv Y, Kramer MR. Pulmonary calcifications: a review. Respir Med 2000; 94 (03) 190-193
    CrossrefPubMedGoogle Scholar
  • 60 Belém LC, Souza CA, Souza Jr AS. , et al. Metastatic pulmonary calcification: high-resolution computed tomography findings in 23 cases. Radiol Bras 2017; 50 (04) 231-236
    CrossrefPubMedGoogle Scholar
  • 61 Masih I, Boyle R, Donnelly A, Soye A, Kidney J. Varicella pneumonitis in an immunocompetent patient. BMJ Case Rep 2011; 2011: bcr0820103259
    PubMedGoogle Scholar
  • 62 Czeyda-Pommersheim F, Hwang M, Chen SS, Strollo D, Fuhrman C, Bhalla S. Amyloidosis: Modern Cross-sectional Imaging. Radiographics 2015; 35 (05) 1381-1392
    CrossrefPubMedGoogle Scholar
  • 63 D'Alessandro C, Piccoli GB, Cupisti A. The “phosphorus pyramid”: a visual tool for dietary phosphate management in dialysis and CKD patients. BMC Nephrol 2015; 16: 9
    CrossrefPubMedGoogle Scholar