Pulmonary alveolar microlithiasis (PAM) is a rare autosomal recessive lung disease characterized by the intra-alveolar accumulation of calcified microliths. It results from mutations in the SLC34A2 gene, which codes for a sodium-dependent phosphate transporter in alveolar type II cells. This prevents the clearance of phosphorus from the alveoli, leading to microlith formation. PAM has no symptoms in many cases, but can cause dyspnea, cough, or respiratory failure from pulmonary fibrosis. Chest imaging shows diffuse micronodular calcifications. Lung biopsy confirms the diagnosis by identifying microliths. There is no cure,

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By
Dr.S.Sesha Sai
Dept of Pulmonary Medicine
SMC, VJA.

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 Rare autosomal recessive disorder.
 Depositional disorder of the lung.
 Intra-alveolar accumulation of spherical calcified
concretions (calciferites, calcospherites, or microliths),
without any calcium metabolism disorder1.
 Presentation - any age, usually occur in third or fourth
decade.

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 Incidental Diagnosis.
 Marcello Malpighi – described in 1868.
 Harbitz – histopathology in 1918. Harbitz Syndrome.2
 Named “Microlithiasis Alveolaris Pulmonum” by Puhr3 in
1933.
 More than 1000 cases have been reported in the world
literature.4

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 Aetiology remains unclear
 Mutations of the SLC34A2 gene considered to be the
cause
 SLC34A2 expressed in alveolar type II cells and
codes for Na-Pi IIb sodium-dependent phosphate
transporter.6,7
 This protein transports the phosphorus ion from the
alveolar space into the alveolar type II cells.

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 As alveolar type II cells are unable to clean up the
phosphorus ion from the alveolar space resulting in its
accumulation and forming microliths rich in calcium
phosphate.
 No sex predilection .5
 NPT2b also expressed in gut, breast, liver, testes,
prostate, kidney, ovaries, pancreas.
 Parental consanguinity will be present in several cases.

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Intra alveolar calcospherites fibrosis
of alveolar wall.
Stones range from 50 to
5000 mm in diameter.
EM - microliths concentric
lamellar, onion skin appearance
Composition : calcium phosphate (2:1)
and small amounts of calcium
10

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 Mostly diagnosed incidentally during
radiography of the chest for other reasons.
 Many patients have no clinical symptoms.
 Dyspnoea, nonproductive cough, chest pain
and asthenia. Hemoptysis and pneumothorax
are also reported.

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 Pulmonary fibrosis, respiratory failure and cor
pulmonale .
 Blood levels of calcium - normal
 Smoking and infection may accelerate disease
progression.

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 The diagnosis can be made with confidence
from the classic radiographic pattern and the
striking radiological and clinical dissociation.
 Isotopic bone imaging tracer studies can
trace the pulmonary uptake of 99m Tc
diphosphonate.

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Fine sand-like calcific
micro nodules
'sandstorm lung',
both lungs, middle
and lower zones
Peripheral,
mediastinal and
fissural, subpleural
calcifications11.
GGOs are common.
Black pleura sign.
Subpleural multiple
small cysts12.

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 Open lung biopsy, needle biopsy,
transbronchial biopsy and
bronchoalveolar biopsy under CT scan
guidance.
 Lung biopsy - most definitive procedure
for confirmation of PAM.
 18-FDG PET in pulmonary alveolar
microlithiasis - inflammatory pathology.

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 Routine blood biochemistry including serum
calcium concentration, hepatic, renal and functions
are usually normal.
 Identification of the SLC34A2 gene mutation.
 Serum concentrations of the surfactant proteins A
and D are elevated - markers to monitor the
activity and progression of the disease.
 Spirometry shows restrictive pattern.

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Testes and
seminal
vesicles 4
Sympatheti
c
ganglia17
Pericardial
calcificatio
n
Pleural
plaques13
Nephrolithi
asis14
Calcific
deposit of
prostate19

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 Lymphocytic interstitial pneumonitis
 Pericardiac cyst
 Non-Hodgkin lymphoma
 Antiphospholipid syndrome
 Discoid lupus, rheumatoid arthritis, psoriasis,
osteopetrosis, Sjogren syndrome
 Hypertrophic pulmonary osteoarthropathy, and pectus
excavatum, diaphyseal aclasis and autosomal recessive
Waardenburg-anophthalmia syndrome.
 Milk alkali Syndrome15

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 No definite treatment is available.
 Home oxygen therapy
 Disodium etidronate - inhibits the micro crystal growth
of hydroxy-apatite - dose of 10 mg / kg per day orally
- 1 year - considerable regression of the calcific
densities21. This therapy remains controversial
given the limited number of reports in the literature .

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 The therapeutic bronchoalveolar lavage (BAL) is not
helpful in PAM unlike PAP.
 Corticosteroids are generally considered to be
ineffective.
 Lung transplantation remains the only possible
treatment for end-stage disease.
◦ The longest survival for PAM treated by transplantation is 15
years without recurrence .
◦ Bilateral lung replacement is preferred.
◦ To date, no recurrence after transplantation has been reported,
confirming that PAM is caused by a local alteration in the
alveolar metabolism.

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 Some authors have reported survival of 20 yrs
 Few cases with a follow-up period of 40 yrs after
the diagnosis have been reported
 However, most cases only have up to 10 yrs of
follow-up time after the initial diagnosis
 Most of the patients of PAM die of progressive
respiratory insufficiency.

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