Pulmonary Alveolar Microlithiasis: A novel patient and brief review
                    of the literature

Mekonnen, Ariana de Oliveira; Schwerk, Nicolaus; Schütz, Katharina; Schramm, Leonie; Dreissig, Anna; Grewendorf, Simon; Sukdolak, Cinja; Dopfer, Christian; Auber, Bernd; Hardenberg, Sandra von; Happle, Christine

doi:10.1055/a-1721-2545

Cited by 1 publication

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“…6 c.524-18_559del p.? TMDs 3–4 NA [ 87 , 92 ] 25 Hom 6 c.560G>A p.Gly187Glu TMD 4 Yes [ 3 ] 26–28 Hom 6 c.575C>A p.Thr192Lys TMD 4 Yes [ 43 ] 29–31 Hom 6 c.593T>C p.Ile198Thr TMD 4 Yes § [ 77 , 95 ] 32 Hom 7 c.646G>T p.Gly216Ter Small IC-loop btw. TMDs 4–5 l Yes [ 3 ] 33–34 Hom 8 c.857_871delins19 p.Ile286LysfsTer29 Large EC-loop NA [ 6 ] 35 Hom 8 c.893_897delTTGTC p.Leu298GlnfsTer14 Large EC-loop NA [ 78 ] 36 Hom 8 …”

Section: The Spectrum Of Allelic Variants In Pammentioning

confidence: 99%

New insights in the genetic variant spectrum of SLC34A2 in pulmonary alveolar microlithiasis; a systematic review

Jönsson

Hilberg

Simonsen

et al. 2023

Orphanet J Rare Dis

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Pulmonary alveolar microlithiasis (PAM) is a rare autosomal recessive lung disease caused by variants in the SLC34A2 gene encoding the sodium-dependent phosphate transport protein 2B, NaPi-2b. PAM is characterized by deposition of calcium phosphate crystals in the alveoli. Onset and clinical course vary considerably; some patients remain asymptomatic while others develop severe respiratory failure with a significant symptom burden and compromised survival. It is likely that PAM is under-reported due to lack of recognition, misdiagnosis, and mild clinical presentation. Most patients are genetically uncharacterized as the diagnostic confirmation of PAM has traditionally not included a genetic analysis. Genetic testing may in the future be the preferred tool for diagnostics instead of invasive methods. This systematic review aims to provide an overview of the growing knowledge of PAM genetics. Rare variants in SLC34A2 are found in almost all genetically tested patients. So far, 34 allelic variants have been identified in at least 68 patients. A majority of these are present in the homozygous state; however, a few are found in the compound heterozygous form. Most of the allelic variants involve only a single nucleotide. Half of the variants are either nonsense or frameshifts, resulting in premature termination of the protein or decay of the mRNA. There is currently no cure for PAM, and the only effective treatment is lung transplantation. Management is mainly symptomatic, but an improved understanding of the underlying pathophysiology will hopefully result in development of targeted treatment options. More standardized data on PAM patients, including a genetic diagnosis covering larger international populations, would support the design and implementation of clinical studies to the benefit of patients. Further genetic characterization and understanding of how the molecular changes influence disease phenotype will hopefully allow earlier diagnosis and treatment of the disease in the future.

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