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PULMONARY ALVEOLAR MICROLITHIASIS(PULAM)

MedGen UID:
56374
Concept ID:
C0155912
Disease or Syndrome
Synonym: Pulmonary Alveolar Microlithiasis
SNOMED CT: Pulmonary alveolar microlithiasis (87153008); Alveolar microlithiasis (87153008); PAM - Pulmonary alveolar microlithiasis (87153008)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
Gene (location): SLC34A2 (4p15.2)
 
Monarch Initiative: MONDO:0009928
OMIM®: 265100
Orphanet: ORPHA60025

Definition

Pulmonary alveolar microlithiasis (PULAM) is a rare disease characterized by the deposition of calcium phosphate microliths throughout the lungs. Most patients are asymptomatic for several years or even for decades, and, generally, the diagnosis is incidental to clinical investigations unrelated to the specific disorder. Cases with early onset or rapid progression are rare. A 'sandstorm-appearing' chest roentgenogram is a typical diagnostic finding. The onset of this potentially lethal disease varies from the neonatal period to old age, and the disease follows a long-term progressive course, resulting in a slow deterioration of lung functions. About one-third of the reported cases are said to be familial (summary by Corut et al., 2006). [from OMIM]

Additional description

From MedlinePlus Genetics
Pulmonary alveolar microlithiasis is a disorder in which many tiny fragments (microliths) of a compound called calcium phosphate gradually accumulate in the small air sacs (alveoli) located throughout the lungs. These deposits eventually cause widespread damage to the alveoli and surrounding lung tissue (interstitial lung disease) that leads to breathing problems. People with this disorder can develop a persistent cough and difficulty breathing (dyspnea), especially during physical exertion. Affected individuals may also experience chest pain that worsens when coughing, sneezing, or taking deep breaths.

Pulmonary alveolar microlithiasis is usually diagnosed before age 40. Often the disorder is discovered before symptoms develop, when medical imaging is done for other reasons. The condition typically worsens slowly over many years, although some affected individuals have signs and symptoms that remain stable for long periods of time.

People with pulmonary alveolar microlithiasis can also develop calcium phosphate deposits in other organs and tissues of the body, including the kidneys, gallbladder, testes, and the valve that connects a large blood vessel called the aorta with the heart (the aortic valve). In rare cases, affected individuals have complications related to accumulation of these deposits, such as a narrowing (stenosis) of the aortic valve that can impede normal blood flow.  https://medlineplus.gov/genetics/condition/pulmonary-alveolar-microlithiasis

Clinical features

From HPO
Progressive pulmonary function impairment
MedGen UID:
341487
Concept ID:
C1849570
Finding
Restrictive ventilatory defect
MedGen UID:
478856
Concept ID:
C3277226
Finding
A functional defect characterized by reduced total lung capacity (TLC) not associated with abnormalities of expiratory airflow or airway resistance. Spirometrically, a restrictive defect is defined as FEV1 (forced expiratory volume in 1 second) and FVC (forced vital capacity) less than 80 per cent. Restrictive lung disease may be caused by alterations in lung parenchyma or because of a disease of the pleura, chest wall, or neuromuscular apparatus.
Intraalveolar nodular calcifications
MedGen UID:
870579
Concept ID:
C4025028
Finding

Professional guidelines

PubMed

Homma S, Ebina M, Kuwano K, Goto H, Sakai F, Sakamoto S, Johkoh T, Sugino K, Tachibana T, Terasaki Y, Nishioka Y, Hagiwara K, Hashimoto N, Hasegawa Y, Hebisawa A; Ministry of Health, Labour and Welfare, the Study Group on Diffuse Pulmonary Disorders, Scientific Research/Research on Intractable Diseases, and Japanese Respiratory Society
Respir Investig 2021 Jan;59(1):8-33. Epub 2020 Jul 2 doi: 10.1016/j.resinv.2020.04.004. PMID: 32622842
Amin SB, Slater R, Mohammed TL
Curr Probl Diagn Radiol 2015 May-Jun;44(3):267-76. Epub 2015 Jan 3 doi: 10.1067/j.cpradiol.2014.12.005. PMID: 25812931
Tachibana T, Hagiwara K, Johkoh T
Curr Opin Pulm Med 2009 Sep;15(5):486-90. doi: 10.1097/MCP.0b013e32832d03bb. PMID: 19617834

Recent clinical studies

Etiology

Cueto-Robledo G, Cantero-Ceballos MD, Gonzalez-Hermosillo LM, Navarro-Vergara DI, Garcia-Cesar M, Torres-Rojas MB, Hernandez-Villa L, Serrato BG, Alfaro-Cruz A
Curr Probl Cardiol 2024 May;49(5):102453. Epub 2024 Feb 9 doi: 10.1016/j.cpcardiol.2024.102453. PMID: 38342349
Homma S, Ebina M, Kuwano K, Goto H, Sakai F, Sakamoto S, Johkoh T, Sugino K, Tachibana T, Terasaki Y, Nishioka Y, Hagiwara K, Hashimoto N, Hasegawa Y, Hebisawa A; Ministry of Health, Labour and Welfare, the Study Group on Diffuse Pulmonary Disorders, Scientific Research/Research on Intractable Diseases, and Japanese Respiratory Society
Respir Investig 2021 Jan;59(1):8-33. Epub 2020 Jul 2 doi: 10.1016/j.resinv.2020.04.004. PMID: 32622842
Sigur E, Roditis L, Labouret G, Bieth E, Simon S, Martin-Blondel A, Michelet M, Mittaine M, Blanchon S
J Pediatr 2020 Feb;217:158-164.e1. Epub 2019 Nov 21 doi: 10.1016/j.jpeds.2019.10.014. PMID: 31761429
Castellana G, Castellana G, Gentile M, Castellana R, Resta O
Eur Respir Rev 2015 Dec;24(138):607-20. doi: 10.1183/16000617.0036-2015. PMID: 26621975Free PMC Article
Prakash UB, Barham SS, Rosenow EC 3rd, Brown ML, Payne WS
Mayo Clin Proc 1983 May;58(5):290-300. PMID: 6341721

Diagnosis

Mittal R, Kumar R, Srikanth JK, Yadav SR, Chandak R, Chakrabarti S
Monaldi Arch Chest Dis 2021 Jun 10;91(4) doi: 10.4081/monaldi.2021.1709. PMID: 34121375
Ufuk F
Radiology 2021 Mar;298(3):567. Epub 2021 Jan 12 doi: 10.1148/radiol.2021203272. PMID: 33434115
Kosciuk P, Meyer C, Wikenheiser-Brokamp KA, McCormack FX
Eur Respir Rev 2020 Dec 31;29(158) Epub 2020 Nov 27 doi: 10.1183/16000617.0024-2020. PMID: 33246992Free PMC Article
Shaw BM, Shaw SD, McCormack FX
Semin Respir Crit Care Med 2020 Apr;41(2):280-287. Epub 2020 Apr 12 doi: 10.1055/s-0040-1702211. PMID: 32279298
Raju S, Ghosh S, Mehta AC
Chest 2017 Jun;151(6):1356-1374. Epub 2017 Feb 16 doi: 10.1016/j.chest.2016.12.033. PMID: 28212835

Therapy

Shaw BM, Shaw SD, McCormack FX
Semin Respir Crit Care Med 2020 Apr;41(2):280-287. Epub 2020 Apr 12 doi: 10.1055/s-0040-1702211. PMID: 32279298
Chopra M, Tendolkar MS, Vardhan V
BMJ Case Rep 2019 Mar 22;12(3) doi: 10.1136/bcr-2018-227406. PMID: 30904891Free PMC Article
Emiralioglu N, Beken B, Ozcan HN, Yalcin E, Dogru D, Ozcelik U, Haliloglu M, Kiper N
Pediatr Int 2016 Aug;58(8):805-7. doi: 10.1111/ped.13032. PMID: 27553891
Saito A, McCormack FX
Clin Chest Med 2016 Sep;37(3):441-8. Epub 2016 Jun 24 doi: 10.1016/j.ccm.2016.04.007. PMID: 27514591Free PMC Article
Ganesan N, Ambroise MM, Ramdas A, Kisku KH, Singh K, Varghese RG
Front Med 2015 Jun;9(2):229-38. Epub 2015 May 30 doi: 10.1007/s11684-015-0394-y. PMID: 26024716

Prognosis

de Oliveira Mekonnen A, Schwerk N, Schütz K, Schramm L, Dreissig A, Grewendorf S, Sukdolak C, Dopfer C, Auber B, von Hardenberg S, Happle C
Klin Padiatr 2022 Sep;234(5):317-319. Epub 2022 Feb 9 doi: 10.1055/a-1721-2545. PMID: 35139546
Mittal R, Kumar R, Srikanth JK, Yadav SR, Chandak R, Chakrabarti S
Monaldi Arch Chest Dis 2021 Jun 10;91(4) doi: 10.4081/monaldi.2021.1709. PMID: 34121375
Kosciuk P, Meyer C, Wikenheiser-Brokamp KA, McCormack FX
Eur Respir Rev 2020 Dec 31;29(158) Epub 2020 Nov 27 doi: 10.1183/16000617.0024-2020. PMID: 33246992Free PMC Article
Castellana G, Castellana G, Gentile M, Castellana R, Resta O
Eur Respir Rev 2015 Dec;24(138):607-20. doi: 10.1183/16000617.0036-2015. PMID: 26621975Free PMC Article
Ferreira Francisco FA, Pereira e Silva JL, Hochhegger B, Zanetti G, Marchiori E
Respir Med 2013 Jan;107(1):1-9. Epub 2012 Nov 23 doi: 10.1016/j.rmed.2012.10.014. PMID: 23183116

Clinical prediction guides

de Oliveira Mekonnen A, Schwerk N, Schütz K, Schramm L, Dreissig A, Grewendorf S, Sukdolak C, Dopfer C, Auber B, von Hardenberg S, Happle C
Klin Padiatr 2022 Sep;234(5):317-319. Epub 2022 Feb 9 doi: 10.1055/a-1721-2545. PMID: 35139546
Oraczewska A, Ochman M, Ograbek-Król M, Kowalska W, Glinka K, Zawadzki F, Barczyk A, Skoczyński S
Wiad Lek 2021;74(9 cz 1):2235-2240. PMID: 34725308
Jönsson ÅLM, Bendstrup E, Mogensen S, Kopras EJ, McCormack FX, Campo I, Mariani F, Escribano-Montaner A, Holm AM, Martinez-Colls MDM, Pintos-Morell G, Taillé C, Crestani B, Hilberg O, Hvarregaard Christensen J, Simonsen U
Eur Respir J 2020 Feb;55(2) Epub 2020 Feb 27 doi: 10.1183/13993003.00806-2019. PMID: 31831582
Sigur E, Roditis L, Labouret G, Bieth E, Simon S, Martin-Blondel A, Michelet M, Mittaine M, Blanchon S
J Pediatr 2020 Feb;217:158-164.e1. Epub 2019 Nov 21 doi: 10.1016/j.jpeds.2019.10.014. PMID: 31761429
Castellana G, Castellana G, Gentile M, Castellana R, Resta O
Eur Respir Rev 2015 Dec;24(138):607-20. doi: 10.1183/16000617.0036-2015. PMID: 26621975Free PMC Article

Recent systematic reviews

Jönsson ÅLM, Hilberg O, Simonsen U, Christensen JH, Bendstrup E
Orphanet J Rare Dis 2023 May 31;18(1):130. doi: 10.1186/s13023-023-02712-7. PMID: 37259144Free PMC Article
Ganesan N, Ambroise MM, Ramdas A, Kisku KH, Singh K, Varghese RG
Front Med 2015 Jun;9(2):229-38. Epub 2015 May 30 doi: 10.1007/s11684-015-0394-y. PMID: 26024716

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