Pulmonary alveolar microlithiasis (PAM)

Pulmonary alveolar microlithiasis is characterised by a marked discrepancy between clinical symptoms and radiological findings. Most patients remain asymptomatic for several years or even decades, and diagnosis by imaging is usually incidental. Over time, a long and progressive course is typically observed, leading to worsening pulmonary function and potentially lung or heart failure. Environmental factors such as smoking or infections appear to accelerate disease progression.

Pulmonary alveolar microlithiasis is a rare disease. Most reported cases originate from Turkey, followed by 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.

Pulmonary alveolar microlithiasis is caused by biallelic pathogenic variants in the SLC34A2 gene (solute carrier family 34 member 2), which encodes a type IIb sodium-phosphate co-transporter. This transporter is expressed, among other tissues, in type II alveolar epithelial cells (AEC II) and is responsible for the uptake of phosphate from the alveolar space released from phospholipids during degradation and recycling of pulmonary surfactant. Defects in this transporter lead to intra-alveolar phosphate accumulation, promoting the formation of calcium-phosphate deposits.

The majority of PAM cases occur sporadically. Up to 40% of cases are familial and are inherited in an autosomal recessive manner.

Pulmonary alveolar microlithiasis is often detected incidentally by imaging due to the discrepancy between clinical presentation and radiological findings. The disease may remain undiagnosed for many years because of prolonged asymptomatic phases.

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