Pulmonary alveolar microlithiasis. State-of-the-art review

Abstract

Pulmonary alveolar microlithiasis (PAM) is a rare genetic lung disease characterized by calcifications within the alveoli. Mutations in the SLC34A2 gene, which encodes a type IIb sodium-phosphate cotransporter, are responsible for this disease, leading to intra-alveolar accumulation of phosphate that favors the formation of microliths. The hallmark of this disorder is clinical-radiological dissociation, with typical imaging findings that correlate well with specific pathological findings. The long-term prognosis is poor and no treatment has been discovered to date. The aim of this review is to describe the main pathological, clinical, and imaging aspects of PAM, ranging from its genetic basis to treatment.

Diseases of Pulmonary Surfactant Homeostasis

“…Pulmonary microlithiasis (OMIM #265100) is a rare disorder in which patients present with dyspnea, interstitial lung disease, and the characteristic micronodular calcifications seen on radiographs and computed tomography (CT) scans (for a review, see 110). It is an autosomal recessive disorder that has been mapped to locus 4p15.31-p15.2, which contains the SLC34A2 gene (OMIM *604217); allelic variants include both deletions and point mutations in this gene (111, 112).…”

“…The microliths gradually grow from smaller to larger structures that eventually fill the entire alveolar space, resulting in injury to the alveolar walls, and are replaced by fibrotic tissue. Recent anecdotal reports support the use of disodium etidronate to treat this rare cause of interstitial lung disease, although lung transplantation has been beneficial (110, 114). …”

A case of pulmonary alveolar microlithiasis associated with a homozygous 195 kb deletion encompassing the entire SLC34A2 gene

“…PAM is a rare disorder in which numerous fragments (microliths) consisting of calcium phosphate gradually accumulate in the alveoli throughout the lungs 2, 3, 4. PAM is an autosomal recessive disorder caused by loss of function mutations in the gene encoding type IIb sodium‐phosphate cotransporter, SCL34A2 .…”

Up-Regulation of Intestinal Phosphate Transporter NaPi-IIb (SLC34A2) by the Kinases SPAK and OSR1

“…NaPi-IIb is primarily expressed in small intestine [39]. Mutations in the SLC34A2 gene may be associated with accumulation of phosphate in lung with development of pulmonary alveolar microlithiasis [40]. SLC34A2 is further expressed in the epididymis and presumably participates in the fine tuning of luminal phosphate concentration [41].…”