ADOPTING ORPHAN DISEASES RARE INTERSTITIAL LUNG DISEASES

adoptingorphandiseaseskapak

PULMONARY ALVEOLAR MICROLITIASIS

Nilüfer Yiğit

Pamukkale University, Faculty of Medicine, Department of Chest Diseases, Denizli, Türkiye

Yigit N. Pulmonary Alveolar Microlitiasis. In: Altinisik G, McCormack FX, editors. Adopting Orphan Diseases: Rare Interstitial Lung Diseases. 1st ed. Ankara: Türkiye Klinikleri; 2025. p.45-59.

ABSTRACT

Pulmonary Alveolar Microlithiasis is a rare, slowly progressive diffuse lung disease characterized by the intra-alveolar accumulation of calcium phosphate microliths. The condition is typically inherited in an autosomal recessive manner and is caused by inactivating mutations in the SLC34A2 gene, which encodes a type IIb sodium-phosphate co-transporter primarily expressed in alveolar type II epithelial cells. The dysfunction of this transporter leads to impaired phosphate clearance from the alveolar space, resulting in the precipitation of hydroxyapatite crystals and the formation of characteristic microliths. Despite its genetic origin being elucidated in recent years, the clinical course of PAM remains unpredictable. Many patients are asymptomatic at the time of diagnosis, which is often made incidentally via chest imaging performed for unrelated reasons. However, the disease tends to progress over time, with patients eventually developing exertional dyspnea, restrictive ventilatory defects, and, in advanced stages, chronic respiratory failure and cor pulmonale. Radiologically, the condition is classically identified by a “sandstorm-like” pattern on chest X-ray, reflecting diffuse, calcified micronodules throughout the lungs. Recent advances in genetics have contributed to a better understanding of disease heterogeneity and genotype-phenotype correlations, yet no treatment has been proven effective in PAM. Empirical therapies, including corticosteroids, bisphosphonates, and whole-lung lavage, have shown limited to no benefit. Lung transplantation remains the only definitive therapeutic option for patients with advanced disease, and early referral before the onset of right heart failure is strongly recommended. This chapter will review the current knowledge on the clinical, radiological, and pathological features of PAM, explore recent insights into its genetic and molecular pathogenesis, and provide an overview of diagnostic strategies, management options, and future research perspectives. Special emphasis will be placed on the role of international registries, telemedicine in follow-up, and emerging concepts in disease monitoring and personalized care.

Keywords: Pulmonary alveolar microlithiasis; SLC34A2 gene mutation; Rare lung disease; Alveolar microliths; Sodium-phosphate cotransporter; Clinical-radiological dissociation; Autosomal recessive disorder; Genetic heterogeneity

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