Pulmonary alveolar microlithiasis: case report and literature review_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

ZHANG Hai ¹ , CHEN Yuqing ¹ , SHEN Yinchen ¹ ,  LI Feng ¹ ,  SHI Jinxiu ²

1. Department of Respiratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, P. R. China;
2. Department of Genetics, Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center and Shanghai Industrial Technology Institute (SITI), Shanghai 201203, P. R. China;

Corresponding author：

LI Feng, Email: lifeng741@aliyun.com; SHI Jinxiu, Email: shijx@chgc.sh.cn

Keywords：

Pulmonary alveolar microlithiasis; Gene analysis; Clinical presentation; Diagnosis; Treatment

DOI：

10.7507/1671-6205.201807036

Video：

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Objective To improve the understanding of pulmonary alveolar microlithiasis (PAM).Methods A male patient and his brother were considered PAM by chest image and further examined by gene sequencing. The patient was confirmed through percutaneous lung biopsy. The clinical data of 172 patients from 108 pieces of literature were collected and reviewed from PubMed. The clinical presentation, radiological character, pathological finding, diagnosis and differential diagnosis, treatment and prognosis of the disease were analyzed and summarized.Results The results of gene sequencing revealed the homozygous mutation of c.910A>T in exon 8 of SLC34A2 gene. The genetic mutation encoding the sodium phosphate co-transporter Npt2b (SLC34A2) was considered as the major pathogenesis. Mutations appeared to cluster in exon 8, c.910A>T was the most common mutation observed in Chinese cases. The most obvious symptoms were dyspnea, followed by cough, chest pain, fever, fatigue, and hemoptysis. The clinical signs consisted of cyanosis, clubbed fingers, moist rales and velcro crackles in the lungs. The typical presentation of PAM on a chest X ray was a ‘sandstorm’ appearance. The most frequent high-resolution CT findings of PAM were diffuse ground-glass attenuation and subpleural linear calcifications. Lung biopsy showed lamellar microliths deposited in alveolar spaces and the pleura. Etidronate had an imprecise role in the treatment of PAM. Lung transplantation was the ultimate effective treatment option.Conclusions PAM is a rare autosomal recessive inherited lung disease. The characteristics of the disease should be fully understood in order to achieve early diagnosis and early intervention. Lung transplantation is recommended for patients of end stage.

Citation： ZHANG Hai, CHEN Yuqing, SHEN Yinchen, LI Feng, SHI Jinxiu. Pulmonary alveolar microlithiasis: case report and literature review. Chinese Journal of Respiratory and Critical Care Medicine, 2019, 18(2): 162-168. doi: 10.7507/1671-6205.201807036 Copy

1.	Harbitz F. Extensive calcification of the lungs as a distinct disease. Arch Intern Med, 1918, 21(1): 139-146.
2.	Puhr L. Mikrolithiasis alveolaris pulmonum. Virchows Archiv für pathologische Anatomie und Physiologie und für klinische Medizin, 1933, 290(1): 156-160.
3.	Saeed RR, Ali KM. A 55 years old man with pulmonary alveolar microlithiasis. Lung India, 2014, 31(3): 293-295.
4.	Jackson KB, Modry DL, Halenar J, et al. Single lung transplantation for pulmonary alveolar microlithiasis. J Heart Lung Transplant, 2001, 20(2): 226.
5.	Castellana G, Castellana G, Gentile M, et al. Pulmonary alveolar microlithiasis: review of the 1022 cases reported worldwide. Eur Respir Review, 2015, 24(138): 607-620.
6.	Lauta VM. Pulmonary alveolar microlithiasis: an overview of clinical and pathological features together with possible therapies. Respir Med, 2003, 97(10): 1081-1085.
7.	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(4): 650-656.
8.	Ferreira FF, Pereira ESJ, Hochhegger B, et al. Pulmonary alveolar microlithiasis. State-of-the-art review. Respir Med, 2013, 107(1): 1-9.
9.	Chan ED, Morales DV, Welsh CH, et al. Calcium deposition with or without bone formation in the lung. Am J Respir Crit Care Med, 2002, 165(12): 1654-1669.
10.	Chu A, Shaharyar S, Chokshi B, et al. Pulmonary alveolar microlithiasis "stone lungs": a case of clinico-radiological dissociation. Cureus, 2016, 8(8): e749.
11.	Deniz O, Ors F, Tozkoparan E, et al. High resolution computed tomographic features of pulmonary alveolar microlithiasis. Eur J Radiol, 2005, 55(3): 452-460.
12.	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(3): 173-181.
13.	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(3): 263-268.
14.	Saito A, Mccormack FX. Pulmonary alveolar microlithiasis. Clin Chest Med, 2016, 37(3): 441-448.
15.	Hashimoto M, Wang D, Kamo T, et al. Isolation and localization of type IIb Na/Pi cotransporter in the developing rat lung. Am J Pathol, 2000, 157(1): 21-27.
16.	Traebert M, Hattenhauer O, Murer H, et al. Expression of type II Na-P_i cotransporter in alveolar type II cells. Am J Physiol, 1999, 277(5 Pt 1): L868-L873.
17.	Khaladkar SM, Kondapavuluri SK, Kamal A, et al. Pulmonary alveolar microlithiasis - clinico-radiological dissociation - a case report with radiological review. J Radiol Case Rep, 2016, 10(1): 14-21.
18.	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): 181r-313r.
19.	Castellana G, Carone D, Castellana M. Microlithiasis of seminal vesicles and severe oligoasthenospermia in pulmonary alveolar microlithiasis (PAM): report of an unusual sporadic case. Int J Fertil Steril, 2015, 9(1): 137-140.
20.	Yin X, Wang H, Wu D, et al. SLC34A2 gene mutation of pulmonary alveolar microlithiasis: report of four cases and review of literatures. Respir Med, 2013, 107(2): 217-222.
21.	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(3): 1205-1214.
22.	Ma TG, Ren J, Yin JZ, et al. A pedigree with pulmonary alveolar microlithiasis: a clinical case report and literature review. Cell Biochem Biophys, 2014, 70(1): 565-572.
23.	Wang HY, Yin XZ, Wu DW, et al. SLC34A2 gene compound heterozygous mutation identification in a patient with pulmonary alveolar microlithiasis and computational 3D protein structure prediction. Meta Gene, 2014, 2: 557-564.
24.	Chatterji R, Gaude GS, Patil PV. Pulmonary alveolar microlithiasis: diagnosed by sputum examination and transbronchial biopsy. Indian J Chest Dis Allied Sci, 1997, 39(4): 263-267.
25.	Monabati A, Ghayumi MA, Kumar PV. Familial pulmonary alveolar microlithiasis diagnosed by bronchoalveolar lavage. A case report. Acta Cytol, 2007, 51(1): 80-82.
26.	Spagnolo P, Rossi G, Trisolini R, et al. Pulmonary sarcoidosis. Lancet Respir Med, 2018, 6(5): 389-402.
27.	Delic JA, Fuhrman CR, Trejo BH. Pulmonary alveolar microlithiasis: AIRP best cases in radiologic-pathologic correlation. Radiographics, 2016, 36(5): 1334-1338.
28.	Griese M. Pulmonary alveolar proteinosis: a comprehensive clinical perspective. Pediatrics, 2017, 140(2): pii: e20170610.
29.	Khorashadi L, Wu CC, Betancourt SL, et al. Idiopathic pulmonary haemosiderosis: spectrum of thoracic imaging findings in the adult patient. Clin Radiol, 2015, 70(5): 459-465.
30.	Ozcelik U, Yalcin E, Ariyurek M, et al. Long-term results of disodium etidronate treatment in pulmonary alveolar microlithiasis. Pediatr Pulmonol, 2010, 45(5): 514-517.
31.	Ozcelik U, Gulsun M, Gocmen A, et al. Treatment and follow-up of pulmonary alveolar microlithiasis with disodium editronate: radiological demonstration. Pediatr Radiol, 2002, 32(5): 380-383.

1. Harbitz F. Extensive calcification of the lungs as a distinct disease. Arch Intern Med, 1918, 21(1): 139-146.
2. Puhr L. Mikrolithiasis alveolaris pulmonum. Virchows Archiv für pathologische Anatomie und Physiologie und für klinische Medizin, 1933, 290(1): 156-160.
3. Saeed RR, Ali KM. A 55 years old man with pulmonary alveolar microlithiasis. Lung India, 2014, 31(3): 293-295.
4. Jackson KB, Modry DL, Halenar J, et al. Single lung transplantation for pulmonary alveolar microlithiasis. J Heart Lung Transplant, 2001, 20(2): 226.
5. Castellana G, Castellana G, Gentile M, et al. Pulmonary alveolar microlithiasis: review of the 1022 cases reported worldwide. Eur Respir Review, 2015, 24(138): 607-620.
6. Lauta VM. Pulmonary alveolar microlithiasis: an overview of clinical and pathological features together with possible therapies. Respir Med, 2003, 97(10): 1081-1085.
7. 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(4): 650-656.
8. Ferreira FF, Pereira ESJ, Hochhegger B, et al. Pulmonary alveolar microlithiasis. State-of-the-art review. Respir Med, 2013, 107(1): 1-9.
9. Chan ED, Morales DV, Welsh CH, et al. Calcium deposition with or without bone formation in the lung. Am J Respir Crit Care Med, 2002, 165(12): 1654-1669.
10. Chu A, Shaharyar S, Chokshi B, et al. Pulmonary alveolar microlithiasis "stone lungs": a case of clinico-radiological dissociation. Cureus, 2016, 8(8): e749.
11. Deniz O, Ors F, Tozkoparan E, et al. High resolution computed tomographic features of pulmonary alveolar microlithiasis. Eur J Radiol, 2005, 55(3): 452-460.
12. 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(3): 173-181.
13. 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(3): 263-268.
14. Saito A, Mccormack FX. Pulmonary alveolar microlithiasis. Clin Chest Med, 2016, 37(3): 441-448.
15. Hashimoto M, Wang D, Kamo T, et al. Isolation and localization of type IIb Na/Pi cotransporter in the developing rat lung. Am J Pathol, 2000, 157(1): 21-27.
16. Traebert M, Hattenhauer O, Murer H, et al. Expression of type II Na-P_i cotransporter in alveolar type II cells. Am J Physiol, 1999, 277(5 Pt 1): L868-L873.
17. Khaladkar SM, Kondapavuluri SK, Kamal A, et al. Pulmonary alveolar microlithiasis - clinico-radiological dissociation - a case report with radiological review. J Radiol Case Rep, 2016, 10(1): 14-21.
18. 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): 181r-313r.
19. Castellana G, Carone D, Castellana M. Microlithiasis of seminal vesicles and severe oligoasthenospermia in pulmonary alveolar microlithiasis (PAM): report of an unusual sporadic case. Int J Fertil Steril, 2015, 9(1): 137-140.
20. Yin X, Wang H, Wu D, et al. SLC34A2 gene mutation of pulmonary alveolar microlithiasis: report of four cases and review of literatures. Respir Med, 2013, 107(2): 217-222.
21. 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(3): 1205-1214.
22. Ma TG, Ren J, Yin JZ, et al. A pedigree with pulmonary alveolar microlithiasis: a clinical case report and literature review. Cell Biochem Biophys, 2014, 70(1): 565-572.
23. Wang HY, Yin XZ, Wu DW, et al. SLC34A2 gene compound heterozygous mutation identification in a patient with pulmonary alveolar microlithiasis and computational 3D protein structure prediction. Meta Gene, 2014, 2: 557-564.
24. Chatterji R, Gaude GS, Patil PV. Pulmonary alveolar microlithiasis: diagnosed by sputum examination and transbronchial biopsy. Indian J Chest Dis Allied Sci, 1997, 39(4): 263-267.
25. Monabati A, Ghayumi MA, Kumar PV. Familial pulmonary alveolar microlithiasis diagnosed by bronchoalveolar lavage. A case report. Acta Cytol, 2007, 51(1): 80-82.
26. Spagnolo P, Rossi G, Trisolini R, et al. Pulmonary sarcoidosis. Lancet Respir Med, 2018, 6(5): 389-402.
27. Delic JA, Fuhrman CR, Trejo BH. Pulmonary alveolar microlithiasis: AIRP best cases in radiologic-pathologic correlation. Radiographics, 2016, 36(5): 1334-1338.
28. Griese M. Pulmonary alveolar proteinosis: a comprehensive clinical perspective. Pediatrics, 2017, 140(2): pii: e20170610.
29. Khorashadi L, Wu CC, Betancourt SL, et al. Idiopathic pulmonary haemosiderosis: spectrum of thoracic imaging findings in the adult patient. Clin Radiol, 2015, 70(5): 459-465.
30. Ozcelik U, Yalcin E, Ariyurek M, et al. Long-term results of disodium etidronate treatment in pulmonary alveolar microlithiasis. Pediatr Pulmonol, 2010, 45(5): 514-517.
31. Ozcelik U, Gulsun M, Gocmen A, et al. Treatment and follow-up of pulmonary alveolar microlithiasis with disodium editronate: radiological demonstration. Pediatr Radiol, 2002, 32(5): 380-383.

Chinese Journal of Respiratory and Critical Care Medicine

Pulmonary alveolar microlithiasis: case report and literature review

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