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Pulmonary Alveolar Microlithiasis (PAM) is a rare, inherited disorder of lung phosphate balance that is associated with small stone formation in the airspaces of the lung. Mutations in the the gene SLC34A2 result in loss of a key sodium, phosphate co-transporter (called Npt2b), known to be expressed in distal airway epithelial cells alveolar type II cells, as well as in the mammary gland, and to a lesser extent in intestine, kidney, skin, prostate and testes. As the disease progresses, the lung fields become progressively more dense (white) on the chest xray, and low oxygen level, lung inflammation and fibrosis, elevated pressures in the lung blood vessels, and respiratory failure ensue, usually in middle age. The clinical course of PAM can be highly variable, with some patients remaining asymptomatic for decades, and others progressing more rapidly. There is no effective treatment, and the mechanisms of stone formation, inflammation and scarring are not known. Signs and symptoms Patients typically have no symptoms until the third or fourth decade of life. In most cases, the disease is discovered incidentally on routine chest Xray. The most common symptoms include the following: * dyspnea * dry cough * chest pain * sporadic hemoptysis * asthenia * pneumothoraces Pathogenesis Type II alveolar cells have many important functions in the lung, including the production of pulmonary surfactant, maintenance of fluid balance and composition in the airspace. Phospholipids are that make up pulmonary surfactant are broken down by macrophages, releasing phosphate into the alveolar lining fluid. The loss of the Npt2b phosphate transported eliminates the ability of alveolar type II cells to pump phosphorus ions from the alveolar space back into the bloodstream, and leads to microlith formation.〔 Genetics PAM is hereditary and another involved family member can be identified in 36% to 61% of cases.〔 Impaired activity of the SLC34A2 gene is responsible for PAM.〔〔 The SLC34A2 gene encodes a membrane protein that is expressed primarily in the apical portions of alveolar type II cells and is the most abundant phosphate carrier in the lungs.〔 Pathology PAM may be confined to certain areas or show diffuse distribution through the lungs.〔 Lung biopsy and autopsy specimens demonstrate characteristic intra-alveolar lamellar microliths.〔 Calcium deposits in the alveoli begin in the lower lobes and spread over a period of years throughout the lungs.〔 Imaging Studies ''Radiology'' Chest radiographs of patients with PAM usually reveal bilateral diffuse micronodular calcifications, producing a "sandstorm” appearance that first involves the inferior portions and then the middle and upper portions of the lungs.〔 ''High-Resolution Computed Tomography'' The most common findings on HRCT are diffuse hyperdense ground-glass attenuation and subpleural linear calcifications, often most predominant in the inferior and posterior portions of the lungs. Additionally, the medial aspects of the lungs appear to be more heavily involved than the lateral aspects.〔 Ground-glass opacities, probably due to small calculi in the air space, are the most common finding in children and in patients with early-stage PAM.〔 ''Magnetic Resonance Imaging'' On magnetic resonance imaging (MRI), the calcific lesions usually show hypointensity or a signal void on T1- and T2-weighted images. Pulmonary Function Studies Pulmonary function tests, arterial blood gases, ventilation perfusion relationships, and O2 diffusing capacity are normal in the initial stages of PAM. As the disease progresses, pulmonary function tests reveal typical features of a restrictive defect with reduced forced vital capacity (FVC) and elevated forced expiratory volume in FEV1/FVC. Diagnosis PAM is usually diagnosed on the basis of a typical radiological pattern, namely a very fine, sand-like micronodulation of calcific density diffusely involving both lungs, with basal predominance. Many authors argue that this pattern precludes the need for a lung biopsy in most cases.〔〔 After PAM is diagnosed in a given patient, family members should be screened by chest radiography, and parents should be counseled that future children are also at risk of developing the disease. Pharmacological Treatment To date, no treatment has been proven to effectively reverse or prevent the progression of PAM. Lung transplantation is an option for end stage disease, but is typically only recommended as a last resort when quality of life is significantly impaired. Etidronate is a bisphosphonate and can reduce the formation of calcium hydroxyapatite crystals. It has led to clinical and radiological improvements in few cases. Epidemiology Since the disease was first described in 1918, over 500 case reports have appeared in the literature. PAM is associated with consanguinity. The incidence is higher in Turkey, Japan, India and Italy. The mean age at diagnosis is 35 years based on the cases reported in the literature. ==References== * * * * 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Pulmonary Alveolar Microlithiasis」の詳細全文を読む スポンサード リンク
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