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Mardani P, Naseri R, Shahriarirad R, Mahram H, Shafi M, Niknam T, Khosravi MB, Fallahi MJ, Amirian A. Successful bilateral lung transplantation in pulmonary alveolar microlithiasis: A case report and review of literature. THE CLINICAL RESPIRATORY JOURNAL 2024; 18:e13773. [PMID: 38725329 PMCID: PMC11082537 DOI: 10.1111/crj.13773] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 03/11/2024] [Accepted: 04/19/2024] [Indexed: 05/13/2024]
Abstract
BACKGROUND Pulmonary alveolar microlithiasis (PAM) is a rare autosomal recessive genetic disorder with approximately 1000 known cases worldwide, in which calcium phosphate microliths deposit in the alveolar air spaces. As of writing this report, no definitive conventional therapy exists, and many PAM cases may progress to severe respiratory failure and potential death. Bilateral lung transplantation (BLx) seems to be the most optimal solution; however, this procedure is challenging along with limited reports regarding the outcome in PAM. We report a case of PAM successfully treated with BLx for the first time in Iran. METHOD We present the case of a 42-year-old female with a longstanding history of cough, not responding to conventional antitussive medication, who was diagnosed as a case of PAM following a hospitalization due to coughing, dyspnea on exertion, and hemoptysis. Despite treatment with corticosteroid and medical treatment, no improvement was achieved and she subsequently developed respiratory and right ventricular failure, with oxygen ventilation dependence. Eventually, she was scheduled for BLx. The operation was successful and during her 2-year follow-up, no recurrence or significant postoperative complications has been reported. CONCLUSION This case presentation and literature review confirm the effectiveness of BLx as a promising treatment for PAM-diagnosed patients, improving both life expectancy and quality of life.
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Affiliation(s)
- Parviz Mardani
- Thoracic and Vascular Surgery Research CenterShiraz University of Medical ScienceShirazIran
- Shiraz Transplant Center, Abu‐Ali Sina HospitalShiraz University of Medical SciencesShirazIran
| | - Reyhaneh Naseri
- Thoracic and Vascular Surgery Research CenterShiraz University of Medical ScienceShirazIran
- School of MedicineShiraz University of Medical SciencesShirazIran
| | - Reza Shahriarirad
- Thoracic and Vascular Surgery Research CenterShiraz University of Medical ScienceShirazIran
- School of MedicineShiraz University of Medical SciencesShirazIran
| | - Hadiseh Mahram
- Student Research Committee, School of MedicineShiraz University of Medical SciencesShirazIran
| | - Masoud Shafi
- Shiraz Transplant Center, Abu‐Ali Sina HospitalShiraz University of Medical SciencesShirazIran
- Department of Cardiac surgery, Abu Ali Sina HospitalShiraz University of Medical SciencesShirazIran
| | - Tahmoores Niknam
- Shiraz Transplant Center, Abu‐Ali Sina HospitalShiraz University of Medical SciencesShirazIran
| | | | | | - Armin Amirian
- Thoracic and Vascular Surgery Research CenterShiraz University of Medical ScienceShirazIran
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2
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Hoseininia S, Salimi M, Salmani A, Jannati R, Negaresh M. Alveolar Microlithiasis with Mild Clinical Symptoms But Severe Imaging Findings: A Case Report. CLINICAL MEDICINE INSIGHTS-CASE REPORTS 2024; 17:11795476241236350. [PMID: 38450045 PMCID: PMC10916495 DOI: 10.1177/11795476241236350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Accepted: 02/12/2024] [Indexed: 03/08/2024]
Abstract
Pulmonary alveolar microlithiasis (PAM) is a rare genetic disorder that causes calcium phosphate microliths to form in the alveoli. Symptoms usually appear in a person's third or fourth decade of life. A definitive diagnosis does not always demand a lung biopsy but can be achieved in families with more than one member with PAM and compatible chest imaging. We present the case of a 47-year-old woman referred to us for shortness of breath. Chest imaging revealed bilateral diffuse ground-glass opacities, interlobar fissure calcification, and subpleural linear calcifications, leading to a diagnosis of PAM. Although there is no specific treatment for this condition, early diagnosis can help prevent it from progressing rapidly by avoiding exposure to risk factors.
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Affiliation(s)
- Saeed Hoseininia
- Department of Internal Medicine (Pulmonary Division), School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Maryam Salimi
- Department of Internal Medicine, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Asma Salmani
- Department of Internal Medicine, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Rona Jannati
- Department of Internal Medicine, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Mohammad Negaresh
- Department of Internal Medicine, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
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Kosciuk P, Meyer C, Wikenheiser-Brokamp KA, McCormack FX. Pulmonary alveolar microlithiasis. Eur Respir Rev 2020; 29:29/158/200024. [PMID: 33246992 PMCID: PMC9488654 DOI: 10.1183/16000617.0024-2020] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Accepted: 07/07/2020] [Indexed: 12/12/2022] Open
Abstract
Pulmonary alveolar microlithiasis (PAM) is a fascinating rare lung disease that is associated with the accumulation of hydroxyapatite microliths within the lumen of the alveolar spaces. In most patients, PAM is discovered incidentally on radiographs performed for other purposes, and the typical disease course is characterised by slowly progressive respiratory insufficiency over decades. Recent genetic analyses that have revealed that the deficiency of the sodium-phosphate cotransporter NPT2B is the cause of PAM have enabled the development of powerful animal models that inform our approach to disease management and treatment. Here we review the epidemiology and molecular pathophysiology of PAM, as well as the diagnostic approach, clinical manifestations, radiographic and pathologic features, and clinical management of the disease. Although there are no proven treatments for PAM, progress in our understanding of disease pathogenesis is providing insights that suggest strategies for trials. A review of the epidemiology and molecular pathophysiology of pulmonary alveolar microlithiasishttps://bit.ly/3lBgM7p
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Affiliation(s)
- Patrick Kosciuk
- Division of Pulmonary, Critical Care, and Sleep Medicine, University of Cincinnati, Cincinnati, OH, USA
| | - Cristopher Meyer
- Division of Radiology, University of Wisconsin, Madison, WI, USA
| | - Kathryn A Wikenheiser-Brokamp
- Division of Pathology & Laboratory Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.,Dept of Pathology & Laboratory Medicine, University of Cincinnati, Cincinnati, OH, USA
| | - Francis X McCormack
- Division of Pulmonary, Critical Care, and Sleep Medicine, University of Cincinnati, Cincinnati, OH, USA
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4
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Agarwal M, Bhalla GS, Sahai K. Pulmonary alveolar microlithiasis: Incidental finding - should we Ignore? AUTOPSY AND CASE REPORTS 2019; 10:e2019133. [PMID: 32039063 PMCID: PMC6945305 DOI: 10.4322/acr.2019.133] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Accepted: 10/15/2019] [Indexed: 12/29/2022] Open
Abstract
Pulmonary alveolar microlithiasis (PAM) is a rare entity, presenting mostly as an incidental finding. This disease has an autosomal recessive inheritance with inactivating mutations in the gene “solute carrier family 34 member 2”. The present study was conducted to bring attention to this rare though preventable disease. The study was a cross-sectional descriptive study, conducted at the Department of Pathology, of a tertiary care hospital in New Dehli-India. PAMs were incidentally seen in two patients diagnosed with micronodular hepatic cirrhosis leading to reanalysis of 212 autopsies, retrospectively. Statistical analysis was done using Stata 14.0. We observed three forms (Type A, B and C) of round hyaline bodies measuring in diameter with thin delicate, radiating fibrils. These bodies were PAS positive, showed black discolouration of the pigment with von Kossa stain and birefringence on polarized microscopy using Congo red stain, however the refringence was light green as compared to apple green birefringence seen with amyloid deposition. PAM has a slow progressive course leading to a high rate of incidental detection. Drugs known to inhibit the micro-crystal growth of hydroxyapatite may slow the disease progression. The family members of patients with PAM may also be kept on follow up with regular imaging. Key messages: It is important to bring out the incidental finding as, seemingly innocuous observations may provide valuable insight into incurable diseases, especially rare diseases.
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Affiliation(s)
- Manisha Agarwal
- Army hospital (R&R), Department of Laboratory Sciences. New Delhi. India
| | | | - Kavita Sahai
- Army hospital (R&R), Department of Laboratory Sciences. New Delhi. India
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5
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Ren XY, Fang XM, Chen JY, Ding H, Wang Y, Lu Q, Ming JL, Zhou LJ, Chen HW. Single-lung transplantation for pulmonary alveolar microlithiasis: A case report. World J Clin Cases 2019; 7:3851-3858. [PMID: 31799314 PMCID: PMC6887609 DOI: 10.12998/wjcc.v7.i22.3851] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Revised: 09/24/2019] [Accepted: 10/05/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Pulmonary alveolar microlithiasis (PAM) is a rare idiopathic lung disease characterized by the accumulation of innumerable microliths. Currently, effective therapeutics for PAM are not available, and the only treatment for end-stage lung disease is lung transplantation (LuTx). Further, there are few reports that focus on LuTx for the treatment of PAM, and the follow-up reports of postoperative imaging are even rarer.
CASE SUMMARY A 52-year-old man presented to Shanghai Pulmonary Hospital in 2017 after experiencing shortness of breath and exacerbation. The patient was diagnosed with PAM and referred for single-LuTx (SLuTx) on March 14, 2018. Preoperative imaging results from a chest X-ray demonstrated bilateral, diffuse, symmetrical, sandstorm-like radiopaque micronodules, and pneumothorax and a computed tomography scan revealed minute, calcified military nodules in both lungs. We performed a left SLuTx, and intraoperative pathology was consistent with PAM. One week after surgery, a chest X-ray revealed slight exudation of the left lung, and one month later, the left transplanted lung exhibited good dilation, mild pulmonary perfusion injury with local infection, and left pleural effusion. Fiberoptic bronchoscopy revealed left hyperplastic granulation at the left bronchial anastomosis. Multiple sputum cultures suggested the presence of Klebsiella pneumoniae and Acinetobacter baumannii. The last follow-up was conducted in April 2019; the patient recovered well.
CONCLUSION This case presents the imaging findings of a patient with PAM before and after LuTx and confirms the effectiveness of LuTx for the treatment of this disease.
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Affiliation(s)
- Xing-Yu Ren
- Department of Radiology, Wuxi People’s Hospital-Nanjing Medical University, Wuxi 214000, Jiangsu Province, China
| | - Xiang-Ming Fang
- Department of Radiology, Wuxi People’s Hospital-Nanjing Medical University, Wuxi 214000, Jiangsu Province, China
| | - Jing-Yu Chen
- Lung Transplantation Center, Wuxi People’s Hospital-Nanjing Medical University, Wuxi 214000, Jiangsu Province, China
| | - Hao Ding
- Lung Transplantation Center, Wuxi People’s Hospital-Nanjing Medical University, Wuxi 214000, Jiangsu Province, China
| | - Yan Wang
- Department of Radiology, Wuxi People’s Hospital-Nanjing Medical University, Wuxi 214000, Jiangsu Province, China
| | - Qiu Lu
- Department of Radiology, Wuxi People’s Hospital-Nanjing Medical University, Wuxi 214000, Jiangsu Province, China
| | - Jia-Lei Ming
- Department of Radiology, Wuxi People’s Hospital-Nanjing Medical University, Wuxi 214000, Jiangsu Province, China
| | - Li-Juan Zhou
- Department of Radiology, Wuxi People’s Hospital-Nanjing Medical University, Wuxi 214000, Jiangsu Province, China
| | - Hong-Wei Chen
- Department of Radiology, Wuxi People’s Hospital-Nanjing Medical University, Wuxi 214000, Jiangsu Province, China
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Alrossais NM, Alshammari AM, Alrayes AM, Mohammad N, Al-Amoodi MJH, Almutairi AM, Alsuhaymi AO, Alhadid DA, Alhammad FA, Ouf NH, Ahmed MH, Saleh W, AlAmodi AA. Pulmonary Hypertension and Polycythemia Secondary to Pulmonary Alveolar Microlithiasis Treated with Sequential Bilateral Lung Transplant: A Case Study and Literature Review. AMERICAN JOURNAL OF CASE REPORTS 2019; 20:1114-1119. [PMID: 31352464 PMCID: PMC6683309 DOI: 10.12659/ajcr.911045] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Patient: Male, 49 Final Diagnosis: Pulmonary alveolar microlithiasis Symptoms: Coughing • shortness of breath Medication: — Clinical Procedure: — Specialty: Surgery
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Affiliation(s)
| | - Abdullah M Alshammari
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.,Department of Thoracic Surgery, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | | | - Najwa Mohammad
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
| | - Mohamed J H Al-Amoodi
- The School of Medicine and Health Sciences, George Washington University, Washington, DC, USA
| | | | | | - Daeya A Alhadid
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
| | | | - Nida H Ouf
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
| | - Mohammed H Ahmed
- Department of Thoracic Surgery, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.,Department of Cardiothoracic Surgery, Ain Shams University, Cairo, Egypt
| | - Waleed Saleh
- Department of Thoracic Surgery, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
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Delic JA, Fuhrman CR, Trejo Bittar HE. Pulmonary Alveolar Microlithiasis: AIRP Best Cases in Radiologic-Pathologic Correlation. Radiographics 2017; 36:1334-8. [PMID: 27618319 DOI: 10.1148/rg.2016150259] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Editor's Note.-RadioGraphics continues to publish radiologic-pathologic case material selected from the American Institute for Radiologic Pathology (AIRP) "best case" presentations. The AIRP conducts a 4-week Radiologic Pathology Correlation Course, which is offered five times per year. On the penultimate day of the course, the best case presentation is held at the American Film Institute Silver Theater and Cultural Center in Silver Spring, Md. The AIRP faculty identifies the best cases, from each organ system, brought by the resident attendees. One or more of the best cases from each of the five courses are then solicited for publication in RadioGraphics. These cases emphasize the importance of radiologic-pathologic correlation in the imaging evaluation and diagnosis of diseases encountered at the institute and its predecessor, the Armed Forces Institute of Pathology (AFIP).
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Affiliation(s)
- Joseph A Delic
- From the Department of Radiology, University of Pittsburgh Medical Center, 200 Lothrop St, Suite 174 E, Pittsburgh, PA 15213
| | - Carl R Fuhrman
- From the Department of Radiology, University of Pittsburgh Medical Center, 200 Lothrop St, Suite 174 E, Pittsburgh, PA 15213
| | - Humberto E Trejo Bittar
- From the Department of Radiology, University of Pittsburgh Medical Center, 200 Lothrop St, Suite 174 E, Pittsburgh, PA 15213
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8
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Abstract
Pulmonary alveolar microlithiasis (PAM) is a genetic lung disorder that is characterized by the accumulation of calcium phosphate deposits in the alveolar spaces of the lung. Mutations in the type II sodium phosphate cotransporter, NPT2b, have been reported in patients with PAM. PAM progresses gradually, often producing incremental dyspnea on exertion, desaturation in young adulthood, and respiratory insufficiency by late middle age. Treatment remains supportive, including supplemental oxygen therapy. For patients with end-stage disease, lung transplantation is available as a last resort. The recent development of a laboratory animal model has revealed several promising treatment approaches for future trials.
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9
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Klikovits T, Slama A, Hoetzenecker K, Waseda R, Lambers C, Murakoezy G, Jaksch P, Aigner C, Taghavi S, Klepetko W, Lang G, Hoda MA. A rare indication for lung transplantation - pulmonary alveolar microlithiasis: institutional experience of five consecutive cases. Clin Transplant 2016; 30:429-34. [PMID: 26841075 DOI: 10.1111/ctr.12705] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/26/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND Pulmonary alveolar microlithiasis (PAM) is a rare lung disease caused by calcifications within the alveolar space. The only known effective treatment for an end-stage PAM is lung transplantation (LuTX). METHODS We performed a retrospective chart review of all individuals that underwent lung transplantation at our center between 1989 and 2013. Five consecutive patients with PAM were identified. RESULTS Four females and one male with a mean age of 46.3 yr were identified. Extracorporeal membrane oxygenation (ECMO) support was required intraoperatively in four cases and post-operatively in one case. Mean post-operative intubation time was 3.3 (range, 2-5) d and mean intensive care unit (ICU) stay was 8.3 (range, 4-12) d. No intraoperative complications were observed. One early patient (operated in 1995) underwent acute re-transplantation on the second post-operative day (POD) and died from sepsis on the 11 POD. In one patient reperfusion edema was observed requiring a prolonged weaning process. No other severe perioperative complications were observed. Four of five patients are currently still alive with normal follow-up parameters. No recurrence of PAM was observed. CONCLUSIONS Lung transplantation is a feasible therapy option in patients with end-stage PAM showing good post-operative results comparable to other indications for LuTX.
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Affiliation(s)
- Thomas Klikovits
- Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria
| | - Alexis Slama
- Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria
| | - Konrad Hoetzenecker
- Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria
| | - Ryuichi Waseda
- Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria
| | - Christopher Lambers
- Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria
| | - Gabriella Murakoezy
- Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria
| | - Peter Jaksch
- Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria
| | - Clemens Aigner
- Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria
| | - Shahrokh Taghavi
- Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria
| | - Walter Klepetko
- Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria
| | - Gyoergy Lang
- Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria.,Department of Thoracic Surgery, Semmelweis University Budapest, Budapest, Hungary
| | - Mir Alireza Hoda
- Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria
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Castellana G, Castellana G, Gentile M, Castellana R, Resta O. Pulmonary alveolar microlithiasis: review of the 1022 cases reported worldwide. Eur Respir Rev 2015; 24:607-20. [PMID: 26621975 PMCID: PMC9487614 DOI: 10.1183/16000617.0036-2015] [Citation(s) in RCA: 90] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2015] [Accepted: 05/18/2015] [Indexed: 12/16/2022] Open
Abstract
Pulmonary alveolar microlithiasis (PAM) is a rare disease characterised by the widespread intra-alveolar accumulation of minute calculi called microliths. It is caused by mutation of the SLC34A2 gene encoding the type IIb sodium phosphate cotransporter in alveolar type II cells. The present study explores the epidemiological, familial, genetic, clinical, diagnostic, radiological and therapeutic aspects with the aim of contributing to a better understanding of this uncommon disease.We searched articles on PAM published up to December 2014 and 544 papers were found, accounting for 1022 cases.PAM is present in all continents and in many nations, in particular in Turkey, China, Japan, India, Italy and the USA. Familiality is frequent. The clinical course is not uniform and the causes of this clinical variability seem to be largely nongenetic. The optimal diagnostic procedure is the association of chest high-resolution computed tomography (HRCT) with bronchoalveolar lavage, but a chest radiograph may suffice in families in which a case has already been diagnosed. Moreover, chest radiography and HRCT allow the classification of the evolutionary phase of the disease and its severity. At present lung transplantation is the only effective therapy. However, better knowledge of the gene responsible offers hope for new therapies.
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Affiliation(s)
| | - Giorgio Castellana
- Institute of Respiratory Disease, Aldo Moro University of Bari, Bari, Italy
| | - Mattia Gentile
- Medical Genetics Unit, Azienda Sanitaria Locale Bari, Bari, Italy
| | | | - Onofrio Resta
- Institute of Respiratory Disease, Aldo Moro University of Bari, Bari, Italy
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Ma T, Ren J, Yin J, Ma Z. A pedigree with pulmonary alveolar microlithiasis: a clinical case report and literature review. Cell Biochem Biophys 2015; 70:565-72. [PMID: 24817643 DOI: 10.1007/s12013-014-9957-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Pulmonary alveolar microlithiasis (PAM) is a rare autosomal recessive disease characterized by the presence of innumerable calcium phosphate microliths in the alveoli. Clinical-radiological dissociation is an important hallmark of this disease. Most PAM patients are asymptomatic and pulmonary tissue changes are discovered incidentally. PAM is pathologically attributable to the formation and aggregation of calcium phosphate microliths in the alveoli after mutations in the SLC34A2 gene (the type IIb sodium-phosphate cotransporter gene) coding NaPi-IIb. In the clinical work, we discovered an inbred pedigree with PAM, which include four PAM siblings. We performed a sequence analysis of the SLC34A2 gene in all members of this PAM pedigree and found that a homozygous mutation c.575C > A (p.T192 K) in exon 6 was involved. To the best of our knowledge, this study was the first to discover nucleotide mutations in exon 6 in Asians.
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Affiliation(s)
- Tiangang Ma
- Department of Respiratory Medicine, Second Hospital of Jilin University, Changchun, 130041, Jilin Province, China
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12
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Ganesan N, Ambroise MM, Ramdas A, Kisku KH, Singh K, Varghese RGB. Pulmonary alveolar microlithiasis: an interesting case report with systematic review of Indian literature. Front Med 2015; 9:229-38. [PMID: 26024716 DOI: 10.1007/s11684-015-0394-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2014] [Accepted: 03/12/2015] [Indexed: 12/31/2022]
Abstract
Pulmonary alveolar microlithiasis is a rare disease characterized by intra-alveolar presence of microliths. This study reports an interesting case of pulmonary alveolar microlithiasis and provides a systematic review of cases reported from India. A 23-year-old female presented with a history of cough, wheeze, chest pain, and episodic wheeze for five months. Pulmonary function tests demonstrated an obstructive pattern, and chest Xray showed fine micronodular opacities predominantly involving the middle and lower zones of both lungs. Transbronchial lung biopsy revealed the diagnosis. She responded well to inhaled steroid therapy. A systematic review of literature was performed and identified 73 cases of pulmonary alveolar microlithiasis reported from India. The mean (SD) age of the patients was 28.8 (14.9) years, with an almost equal male:female ratio. Many patients were asymptomatic at presentation. Breathlessness and cough were the most common symptoms, and the disease progressed into respiratory failure associated with cor pulmonale. About one-third of the cases were initially misdiagnosed and treated as pulmonary tuberculosis. Extra-pulmonary manifestations and comorbidities were also evident in our series. This systematic review helps to determine epidemiological and clinical characteristics of pulmonary alveolar microlithiasis. Further research is needed to elucidate the etiopathogenesis, diagnosis, and therapeutic options, which are beneficial in developing and identifying cost-effective treatment for pulmonary alveolar microlithiasis.
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Affiliation(s)
- Nidhya Ganesan
- Department of Pathology, Pondicherry Institute of Medical Sciences, Pondicherry, 605014, India,
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13
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Abstract
Pulmonary alveolar microlithiasis (PAM) is a rare, chronic lung disease with bilateral intra-alveolar calcium and phosphate deposition throughout the lung parenchyma with predominance to lower and midzone. Although, etiology and pathogenesis of PAM is not fully understood, the mutation in SLC34A2 gene that encodes a sodium-phosphate co-transporter in alveolar type II cells resulting in the accumulation and forming of microliths rich in calcium phosphate (due to impaired clearance) are considered to be the cause of the disease. Chest radiograph and high-resolution CT of thorax are nearly pathognomonic for diagnosing PAM. HRCT demonstrates diffuse micronodules showing slight perilobular predominance resulting in calcification of interlobular septa. Patients with PAM are asymptomatic till development of hypoxemia and cor-pulmonale. No therapy has been proven to be beneficial except lung transplantation.
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Affiliation(s)
- Surender Kashyap
- Department of Pulmonary Medicine, Kalpana Chawla Government Medical College, Karnal, Haryana, India
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14
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Siddiqui NA, Fuhrman CR. Best cases from the AFIP: Pulmonary alveolar microlithiasis. Radiographics 2011; 31:585-90. [PMID: 21415198 DOI: 10.1148/rg.312105157] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
- Nasir A Siddiqui
- Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
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15
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Samano MN, Waisberg DR, Canzian M, Campos SV, Pêgo-Fernandes PM, Jatene FB. Lung transplantation for pulmonary alveolar microlithiasis: a case report. Clinics (Sao Paulo) 2010; 65:233-236. [PMID: 20186308 PMCID: PMC2827711 DOI: 10.1590/s1807-59322010000200016] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Affiliation(s)
- Marcos Naoyuki Samano
- Thoracic Surgery Division, Heart Institute (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - São Paulo/SP, Brazil
| | | | - Mauro Canzian
- Pathology Division, Heart Institute (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - São Paulo/SP, Brazil
| | - Silvia Vidal Campos
- Lung Transplant Group, Heart Institute (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - São Paulo/SP, Brazil,
, Tel.: 55 11 3069.5248
| | - Paulo M. Pêgo-Fernandes
- Thoracic Surgery Division, Heart Institute (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - São Paulo/SP, Brazil
| | - Fabio B. Jatene
- Thoracic Surgery Division, Heart Institute (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - São Paulo/SP, Brazil
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16
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Abstract
PURPOSE OF REVIEW Our knowledge of pulmonary alveolar microlithiasis (PAM) has significantly increased since its detailed description by Sosman in 1957. Here we provide updated information on the long-term clinical course, the specific findings in imaging studies and the genetics of this disease. RECENT FINDINGS The responsible gene, the mutation of which is associated with PAM, has been identified as SLC34A2. Characteristic chest computed tomography (CT) findings in patients with PAM have been shown to correlate well with specific pathological findings. Elevated serum levels of surfactant proteins A and D have also been reported in this disease. Long-term follow up information has been updated. SUMMARY The gene responsible for PAM, SLC34A2, has been identified. It encodes a type IIb sodium-dependent phosphate transporter, the function of which provides an insight into the pathogenesis of this disease. The demonstration of a mutation in the SLC34A2 gene helps to confirm the diagnosis of PAM. Characteristic chest CT findings that include irregular thickening of perilobular interstitium and calcification along perilobular structures correlate with specific pathological findings. Serum levels of surfactant proteins A and D correlate with the progression of the disease, and may be a useful monitoring tool. Scrutiny of the long-term follow-up data of PAM patients reveals that the prognosis for PAM is poor. The establishment of an effective treatment, which is not yet available, is mandatory.
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17
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“Sandstorm” image: bone scintigraphy in pulmonary alveolar microlithiasis. Eur J Nucl Med Mol Imaging 2009; 36:1353. [DOI: 10.1007/s00259-009-1137-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2009] [Accepted: 03/25/2009] [Indexed: 12/28/2022]
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Shigemura N, Bermudez C, Hattler BG, Johnson B, Crespo M, Pilewski J, Toyoda Y. Lung transplantation for pulmonary alveolar microlithiasis. J Thorac Cardiovasc Surg 2009; 139:e50-2. [PMID: 19660326 DOI: 10.1016/j.jtcvs.2008.07.066] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2008] [Accepted: 07/05/2008] [Indexed: 12/16/2022]
Affiliation(s)
- Norihisa Shigemura
- Cardiopulmonary Transplantation, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
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19
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Sampsonas F, Karkoulias K, Kaparianos A, Tsiamita M, Spiropoulos K. Pulmonary alveolar microlithiasis in a patient with rheumatic valvular heart disease. Am J Med Sci 2007; 334:128-30. [PMID: 17700203 DOI: 10.1097/maj.0b013e31812e4bbd] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Pulmonary alveolar microlithiasis is a rare disease characterized by widespread intra-alveolar calcification of both lungs that is asymptomatic in the early stages. The disease typically follows a protracted course, and death can occur in 5 to 41 years after the initial diagnosis. Rheumatic fever is a multisystemic inflammatory disease that afflicts the child and juvenile population, and it is still very common in developing countries. Valve failure is the condition most linked to increased morbidity and mortality rates in this population and is the most severe complication of rheumatic fever, with consequent onset of chronic heart valve disease. We present a case of a female patient with a potential diagnosis of pulmonary alveolar microlithiasis with concurrent rheumatic valvular disease.
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Affiliation(s)
- Fotis Sampsonas
- Department of Internal Medicine, Division of Pneumology, University Hospital of Rio--Patras, Patras, Greece
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Affiliation(s)
- R Agarwal
- Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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21
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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. [PMID: 16635094 DOI: 10.1111/j.1440-1843.2006.00844.x] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Pulmonary alveolar microlithiasis (PAM) is a rare disease characterized by widespread localization of calcispherites in the alveolar spaces. The authors report two cases of PAM, with markedly elevated sera concentrations of surfactant protein-A and surfactant protein-D, which showed a tendency to increase as the disease progressed. Therefore, surfactant protein-A and surfactant protein-D may function as serum markers to monitor the disease activity and progression of PAM.
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Affiliation(s)
- Hiroki Takahashi
- The Third Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
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22
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Kacmaz F, Alyan O, Celenk M, Ozdemir O, Turkvatan A, Dogan M, Ilkay E. A case of pulmonary alveolar microlithiasis with cardiac constriction secondary to severe adjacent pleural involvement. Cardiology 2006; 107:213-6. [PMID: 16946600 DOI: 10.1159/000095420] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2006] [Accepted: 06/10/2006] [Indexed: 11/19/2022]
Abstract
Pulmonary alveolar microlithiasis (PAM) is a rare disorder of uncertain etiology and pathogenesis that is characterized by tiny calcium phosphate depositions in lung alveoli. Ectopic organ involvement has been reported infrequently. We hereby present a patient with PAM complicated by severe pleural calcification that has caused a constrictive cardiac physiology, a heretofore unknown occurrence/association. Based on our observations in this particular case, we suggest that a non-invasive echocardiographic examination may be well worth in the investigation of PAM patients in whom symptom onset at an early age has occurred, particularly if severe pleural calcification adjacent to the heart is present.
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Affiliation(s)
- Fehmi Kacmaz
- Department of Cardiology, Turkiye Yuksek Ihtisas Hospital, Ankara, Turkey.
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23
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Deniz O, Ors F, Tozkoparan E, Ozcan A, Gumus S, Bozlar U, Bilgic H, Ekiz K, Demirci N. High resolution computed tomographic features of pulmonary alveolar microlithiasis. Eur J Radiol 2005; 55:452-60. [PMID: 16129256 DOI: 10.1016/j.ejrad.2005.01.010] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2004] [Revised: 01/03/2005] [Accepted: 01/05/2005] [Indexed: 02/07/2023]
Abstract
BACKGROUND Pulmonary alveolar microlithiasis (PAM) is a rare, chronic lung disease with unknown etiology and with a nonuniform clinical course. Nonuniformity of clinical course might be related to the degree of pulmonary parenchymal alterations, which can be revealed with high resolution computed tomography (HRCT). However, HRCT findings of PAM were not fully described in the current literature. AIM The aim of this study was to interpret and to contribute to describe HRCT findings of PAM and to investigate a correlation between profusion of micro nodules (MN) and pulmonary parenchymal alterations in patients with PAM. MATERIAL AND METHODS Ten male patients with PAM (mean age: 22+/-3.2) were included into the study. HRCT images were assessed for patterns, distribution, and profusion of pulmonary abnormalities. Dividing the lungs into three zones, profusion of abnormalities was assessed. A profusion score (1-4) was given and the scores of each zone were then summed to obtain a global profusion score for HRCT ranging from 0 to 12. Also a parenchymal alteration score (PAS) was defined with respect to profusion of abnormalities. Chest X-rays were also scored. RESULTS All of ten patients with PAM had findings of interstitial lung disease in varying degrees on their HRCTs. HRCT findings of patients with PAM were as following: MN, parenchymal bands (PB), ground glass opacity (GGO) and, sub pleural interstitial thickening (SPIT) in 10 patients; interlobular septal thickening (ILST), in 9 patients; paraseptal emphysema (PSA) in 8 patients; centrilobular emphysema (CLA) in 7 patients; bronchiectasis (BE), confluent micro nodules (CMN) in 6 patients; peri bronchovascular interstitial thickening (PBIT) in 5 patients; panacinar emphysema (PANAA) in 3 patients; pleural calcification (PC) in 2 patients. A significant correlation between MN scores and PAS (r=0.68, p=0.031, MN scores and GGO scores (r=0.69, p=0.027) and, MN scores and CLA scores (r=0.67, p=0.034) was detected. We also found significant correlations between HRCT scores and results of pulmonary function tests (PFTs), HRCT scores and chest X-ray score (CXRS) and, CXRS and results of PFTs. CONCLUSION We conclude that patients with PAM may have all findings of interstitial lung disease in varying degrees as well as MNs on their HRCTs. More importantly, this study suggests a proportional relationship between profusion of MNs and parenchymal alterations in patients with PAM. This study also suggests that the degree of parenchymal alterations closely related with the degree of pulmonary function loss in patients with PAM.
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Affiliation(s)
- Omer Deniz
- Pulmonary Medicine and Tuberculosis, Gulhane Military Medical Academy, Etlik, Ankara 06018, Turkey.
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24
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Sahin U, Yildiz M, Bircan HA, Akkaya A, Candir O. Absence of pulmonary uptake of Tc-99m methylenediphosphonate in alveolar microlithiasis. Ann Nucl Med 2005; 18:695-8. [PMID: 15682851 DOI: 10.1007/bf02985964] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Pulmonary alveolar microlithiasis (PAM) is a rare disease of unknown etiology characterized by accumulation of calcific concretions in the alveolar spaces. The paper reports a case of PAM in a 56-year-old male. The patient had persistent dry cough, and gradually progressive dyspnea on exertion. The diagnosis was established on the basis of roentgenography and confirmed by the sputum and transbronchial biopsy findings. Scintigraphy revealed the absence of Tc-99m methylenediphosphonate uptake of lungs. Familial occurrence was not observed. Chest roentgenogram, pulmonary function, and clinical status of the patient have remained stable for 41 months. Radiological and clinical follow-up of the disease continues.
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Affiliation(s)
- Unal Sahin
- Department of Lung Disease, School of Medicine, Südeyman Demirel University, Isparta, Turkey.
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25
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Castellana G, Gentile M, Castellana R, Fiorente P, Lamorgese V. Pulmonary alveolar microlithiasis: clinical features, evolution of the phenotype, and review of the literature. AMERICAN JOURNAL OF MEDICAL GENETICS 2002; 111:220-4. [PMID: 12210357 DOI: 10.1002/ajmg.10530] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Pulmonary alveolar microlithiasis (PAM) (MIM 265100) is a rare, autosomal recessive pneumopathy characterized by intra-alveolar formation and accumulation of tiny, roundish corpuscles called "microliths". The name "alveolar microlithiasis" was first used by Puhr in 1933; since then, several reports have appeared, and over 300 individuals with this condition have been reported. We have reviewed the PAM cases in the literature in light of personal experience, focusing on medical implications, disease diagnosis and progression over time, familial predisposition, and geographical and sex distribution. This study confirms autosomal recessive inheritance and does not support the role of other, non-genetic, factors in the pathogenesis of PAM.
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Affiliation(s)
- G Castellana
- Department of Chest Diseases, Hospital Santa Maria degli Angeli, Putignano, Bari, Italy
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Abstract
Interstitial lung disease is a heterogeneous group of illnesses, some of which may progress to a fibrosing stage and cause respiratory failure. For selected candidates, lung transplantation is the ultimate therapeutic option. We review data on lung transplantation for various interstitial lung diseases. We address indications, procedures, and outcomes for patients undergoing transplantation. Unique issues affecting morbidity, mortality, and recurrence of disease are discussed. We review the literature of transplantation for specific interstitial lung diseases and the outcomes of transplantation for interstitial lung diseases. Candidates with idiopathic pulmonary fibrosis experience high mortality on the waiting list, but derive significant survival benefit from lung transplantation. Recurrence is reported for several interstitial lung diseases after lung transplantation. Survival with lung transplantation for interstitial lung diseases is comparable with that attained in recipients with other indications. Lung transplantation is a well-tolerated, effective therapy for respiratory failure in interstitial lung disease.
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Affiliation(s)
- R Sulica
- Mount Sinai School of Medicine, One Gustave Levy Place, New York, NY 10029, USA
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Mennecier D, Debourdeau P, Minvielle F, Frouget T, Pats B, Rouvier B. [Diffuse pulmonary calcification]. Rev Med Interne 1999; 20:715-7. [PMID: 10480177 DOI: 10.1016/s0248-8663(99)80494-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Affiliation(s)
- D Mennecier
- Service de réanimation, hôpital d'instruction des armées Percy, Clamart, France
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