Pulmonary alveolar microlithiasis: A case report with a novel mutation in the SLC34A2 gene and review of the literature

Simon, Caroline T.; Lewis, Toby C.; Neemuchwala, Fatima; Arteta, Manuel; Rabah, Raja

doi:10.1016/j.ehpc.2018.04.004

Cited by 6 publications

(11 citation statements)

References 8 publications

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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%

“…Normal physical findings and exercise capacity at age 27 No [ 5 , 32 , 111 ] 18 F, 43/43 TUR – Exertional dyspnoea, cough (−) – Suspicious familial history of PAM [ 76 ] c.316G>A ‡ + c.1238G>A ‡ 19 F, 39/22 USA Yes Dyspnoea, chest pain (−) No [ 3 ] c.380-345_c.523+659del † 20 (sib 1) 21 (sib 2) F, 40/40 F, (adult) § / – CHI Yes Progressive dyspnoea (37) No No – [ 86 ] c.448G>A + c.524-1G>C 22 M, 8/ – CHI No No – [ 94 ] c.524-18_559del † 23 M, 1/1 UGA Yes Progressive dyspnoea developing to severe respiratory distress and hypoxaemia (2 mos.) – Adopted [ 87 ] 24 F, 16/16 EAF – Recurrent dizziness, occasional cough upon physical stress and epigastric pain (−) …”

Section: The Spectrum Of Allelic Variants In Pammentioning

confidence: 99%

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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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Section: The Spectrum Of Allelic Variants In Pammentioning

confidence: 99%

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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“…26 PAM is typically slowly progressive, with respiratory failure developing in middle age, but there is considerable variability with reports of relatively mild disease in octogenarians 9 and explosive onset and rapid progression in infants and children. 27 Dyspnea on exertion is the most common symptom/sign, but cough, chest pain, hemoptysis, and pneumothorax also occur. 1 Pulmonary function testing (PFT) is usually normal in the initial stages of PAM; however, as disease progresses, patients often develop a restrictive defect with a reduction in total lung capacity and diffusing capacity for carbon monooxide.…”

Section: Clinical Characteristicsmentioning

confidence: 99%

Pulmonary Alveolar Microlithiasis

Shaw

McCormack

2020

Semin Respir Crit Care Med

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Pulmonary alveolar microlithiasis (PAM) is a rare, autosomal recessive disorder that is caused by mutations in SCL34A2 that encodes for the type IIb sodium-dependent phosphate cotransporter (Npt2b). The loss of Npt2b transporter function from alveolar epithelial cells results in failure to export inorganic phosphate from the alveolar lining fluid, which then accumulates, binds to calcium, and forms hydroxyapatite microliths. Radiographs and computed tomography of the chest demonstrate hyperdense infiltrates that are often quite dramatic and distinctive, and in many cases, the diagnosis can be made without invasive measures. The most common presenting symptom of PAM is dyspnea on exertion, but the disease is frequently first noted as an incidental finding in asymptomatic patients who have chest films performed for unrelated reasons. Pulmonary fibrosis, pulmonary hypertension, and respiratory failure can develop as the disease progresses, and treatment remains supportive. Lung transplantation is an option for those with end stage disease.

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“…Pulmonary alveolar microlithiasis (PAM) is an autosomal recessive disease of the lung, characterized by diffuse deposits of intra-alveolar calcium phosphate microliths [ 1 ]. It affects both sexes and has been reported in all ages, occurring mostly in the second and third decades.…”

Section: Introductionmentioning

confidence: 99%

Pulmonary Alveolar Microlithiasis in a Middle-Aged Man Presenting With Respiratory Failure: A Case Report and Review of the Literature

Omo-Ogboi,

Ederhion,

Ur Rehman

et al. 2024

Cureus

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Pulmonary alveolar microlithiasis (PAM) is an autosomal recessive disease of the lung, characterized by diffuse deposits of intra-alveolar calcium phosphate microliths. It usually affects both sexes, presenting mostly in the second and third decades. The clinical course is highly variable, ranging from being asymptomatic to respiratory failure. PAM is usually diagnosed after careful clinical, radiological, and pathological evaluation, usually when patients present for other medical purposes. Here, a case of PAM in a middle-aged man presenting with acute-on-chronic hypoxemic respiratory failure is reported, with a review of the literature.

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Pulmonary alveolar microlithiasis: A case report with a novel mutation in the SLC34A2 gene and review of the literature

Cited by 6 publications

References 8 publications

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

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

Pulmonary Alveolar Microlithiasis

Pulmonary Alveolar Microlithiasis in a Middle-Aged Man Presenting With Respiratory Failure: A Case Report and Review of the Literature

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