Abstract
Pulmonary alveolar microlithiasis (PAM) is a rare autosomal recessive lung disease in which calcium phosphate microliths fill the alveoli. Although the cause of it remained unknown for some time, more recently loss-of-function variants in SLC34A2, which encodes the sodium-phosphate cotransporter NPT2b, explain nearly all genetically tested cases; failure to clear phosphate from the alveolar lining fluid leads to microlith formation, and an epithelial Npt2b-knockout mouse reproduces the human phenotype. Diagnosis now rests mainly on characteristic high-resolution CT and, increasingly, on genotyping rather than lung biopsy. The protracted course has been described in some series of cases, with death from respiratory failure. No drug has proven efficacy; lung transplantation is the only established therapy, and no allograft recurrence has been documented. Preclinical data support phosphate restriction, EDTA lavage and gene-directed approaches. However, controlled trials with more genotype-phenotype correlation and prospective natural-history data are still needed.