PULMONARY ALVEOLAR MICROLITHIASIS: A LITERATURE REVIEW AND CASE REPORT OF A LUNG BIOPSY-CONFIRMED DISEASE IN AN INFANT

The article provides up-to-date information on epidemiology, etiology, genetics, pathogenesis, pathomorphology, clinical manifestation, X-ray and computed tomography (CT) semiotics, features in childhood, treatment of a rare genetic interstitial lung disease – pulmonary alveolar microlithiasis (PAM). A clinical observation of a child with PAM manifestation, confirmed by lung biopsy in infancy, is presented. The results of X-ray and CT of the patient's chest organs are presented, the unique features of the course of the disease are listed.

Novel insights into pulmonary phosphate homeostasis and osteoclastogenesis emerge from the study of pulmonary alveolar microlithiasis.

Pulmonary alveolar microlithiasis (PAM) is an autosomal recessive lung disease caused by a deficiency in the pulmonary epithelial Npt2b sodium-phosphate co-transporter that results in accumulation of phosphate and formation of hydroxyapatite microliths in the alveolar space. The single cell transcriptomic analysis of a PAM lung explant showing a robust osteoclast gene signature in alveolar monocytes and the finding that calcium phosphate microliths contain a rich protein and lipid matrix that includes bone resorbing osteoclast enzymes suggested a role for osteoclast-like cells in the defense against microliths. While investigating the mechanisms of microlith clearance, we found that Npt2b modulates pulmonary phosphate homeostasis through effects on alternative phosphate transporter activity and alveolar osteoprotegerin, and that microliths induce osteoclast formation and activity in a receptor activator of nuclear factor-κB ligand (RANKL) and dietary phosphate dependent manner. This work reveals that Npt2b and pulmonary osteoclast-like cells play key roles in pulmonary homeostasis and suggest potential new therapeutic targets for the treatment of lung disease.

Pulmonary Alveolar Microlithiasis - Report of Two New Cases and Review of the Literature

INTRODUCTION: Pulmonary alveolar microlithiasis (PAM) is a rare autosomal recessive disease characterized by the intra-alveolar accumulation of spherical calcified microliths, of a phospho-calcium nature, in the absence of any problem of phosphocalcium metabolism. The majority of patients are asymptomatic. The disease is often diagnosed on routine radiological examination.CASE REPORTS: We report two cases of PAM; A 17-year-old girl with three generations of consanguinity, who consulted for bronchial syndrome. Auscultation revealed very fine diffuse ronchi. The X-ray showed a bilateral alveolar syndrome, especially on the right, a bilateral bronchointerstitial syndrome, and diffuse bilateral calcifications. The thoracic CT scan showed calcified micro and macronodules with thickening of the septa, middle section involvement with fibrosing remodeling, fibrosis, and tractional bronchiectasis of the bases, pleural and pericardial calcifications. Respiratory function tests showed a restrictive syndrome with a vital capacity of 70% and normal GDS. This radiological and scanographic picture made us think of PAM. We then decided to carry out a family investigation with chest radiographs. All family members had normal radiographs, except for a sister who was three years old, with no particular history, no functional respiratory signs, and no particular complaints. Her chest radiograph showed the famous sandstorm appearance of microcalcifications, with pulmonary distension at the apexes and retractions at the bases. Spirometry and blood gases were normal. Chest CT found microcalcifications, with bilaterally distributed and diffuse ground-glass aspects, with a slight right-hand predominance.CONCLUSION: MLA is known to be radio-clinically dissociative. The diagnosis can be made by radiology alone in typical cases; sometimes, Transbronchial or surgical lung biopsies are needed. The prognosis is compromised in the long term. The only effective treatment nowadays is lung transplantation.

Pulmonary Alveolar Microlithiasis and Pregnancy - A Case Report

Pulmonary alveolar microlithiasis (PAM) is a rare autosomal recessive disease with a high penetrance characterized by widespread intra-alveolar accumulation of innumerable minute calculi called microliths. Pregnancy with PAM is even rarer. Here we are presenting the second case in India of 28yrs G2P1L1 37 weeks 1 day, known case of PAM with gestational hypothyroidism. She had difficulty in breathing which has increased from NYHA- grade II to NYHA- grade III from the fifth month of gestation. She had parrot beak (grade 3) clubbing. She was having intrauterine growth restriction with a growth discrepancy of four weeks. The patient was taken for cesarean section in view of a breech with premature rupture of the membrane with intrauterine growth restriction. Since lung function is compromised, oxygen supply to the baby is expected to be compromised, which can lead to intrauterine growth restriction, which is evident in this patient in both of her pregnancies.

Pulmonary alveolar microlithiasis: Blizzard of lung

Pulmonary alveolar microlithiasis (PAM) is a rare inherited disorder in which patients present with either nonspecific signs and symptoms or are asymptomatic. Clinical-radiological dissociation is a commonly seen feature of the disease. Majority of cases are diagnosed in second and third decade of life, although presentation in paediatric and elderly population is also reported. Pathognomonic radiological findings, with normal calcium and phosphate levels can confirm the diagnosis without the need of further investigations in large number of cases. A high index of suspicion and knowledge of the disease is of paramount importance as it has a wide range of presentation and variable course thus posing a diagnostic challenge. We present two cases of this rare disease in elderly females with distinct presentations although with similar and characteristic radiological findings along with a brief review of literature of the disease.

Pulmonary Alveolar Microlithiasis and Rheumatoid Arthritis: A Case Report and Review of the Literature

Pulmonary alveolar microlithiasis is a rare autosomal recessive condition that is characterized by the formation of excessive calcium phosphate microliths in the alveoli. Most patients are diagnosed in adulthood due to the slow progression of the disease. Children with this disease are asymptomatic, and changes in the lung parenchyma are usually discovered incidentally. The diagnosis is made by the combination of a positive chest imaging and histological examination. Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by chronic seropositive symmetrical inflammatory polyarthritis with numerous extra-articular manifestations. It targets the lining of the synovial membranes, frequently affects females more than males, and is treated with the disease-modifying antirheumatic drugs (DMARDs). If left untreated, it leads to increased morbidity, mortality, and socioeconomic burdens. In this case, we report a 19-year-old young man who presented with clinical and radiographic features of PAM associated with RA.