SCIENTIFIC BACKGROUND

SLC34A2

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SCIENTIFIC BACKGROUND

Pulmonary alveolar microlithiasis (PAM) is a rare lung disease characterized by deposition of calcium-phosphate crystals, called microliths, in the alveoli. The hallmark of the disease is the discrepancy between clinical and radiological findings. Most patients are asymptomatic for several years or even decades, and the detection of PAM by imaging is usually an incidental finding. A long and progressive course is most often described, leading to deterioration of pulmonary function and even lung or heart failure. Environmental factors such as smoking or infection seem to accelerate the progression of the disease. The long-term prognosis is poor, and therapy - apart from lung transplantation - is currently not available.

 

Biallelic pathogenic variants of the SLC34A2 (solute carrier family 34 member 2) gene, which encodes a type IIb sodium-phosphate co-transporter, are causative for the disease. The transporter is expressed in type II alveolar epithelial cells (AEC II), among others, and is responsible for the uptake of phosphate from the alveolar space that is released from phospholipids during the degradation and recycling of pulmonary surfactant. Defects in the transporter lead to intra-alveolar accumulation of phosphate, which promotes the formation of calcium-phosphate deposits. The majority of cases occur sporadically, and up to 40% of cases are familial and inherited in an autosomal recessive pattern. Most cases have been described in Turkey, China, Japan, India, Italy, and the United States (in descending order). The prevalence of pathogenic PAM variants in the Japanese population has been estimated to be less than 0.008.

 

References

Stamatopoulos et al. 2017, Respir Med Case Rep 22:24 / Saito et al. 2016, Clin Chest Med 37:441 / Castellana et al. 2015, Eur Respir Rev 24:607 / Ferreira et al. 2013, Respir Med 107:1 / Huqun et al. 2007, Am J Respir Crit Care Med 175:263

GENES
SLC34A2
ASSOCIATED TESTS
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