Introduction
Pulmonary
alveolar microlithiasis (PAM) is an uncommon, autosomal recessive lung
disease with high penetrance (OMIM #265 100) and is considered to be a
monogenic disorder. 1 The only known pathogenic gene
is solute carrier family 34 member 2 (SLC34A2) (Entrez Gene ID
10568).2-4 SLC34A2 mutations lead to the accumulation
of calcium phosphate in the alveoli, restrict alveolar dilatation, and
then progress to a restrictive lung function complicated with reduced
dynamic and static volumes.5, 6 Dyspnea is the most
frequent symptom, followed by dry cough, chest pain, asthenia,
pneumothorax, pulmonary fibrosis, and
cor pulmonale.7-10While children are always in the onset at the early stage of PAM and
usually remain asymptomatic when diagnosed; however, some can present
with dry cough, exertional dyspnea, and chronic hypoxic signs, including
clubbing.3 Recently, some complications with PAM have
been reported, such as asthma, pneumomediastinum, subcutaneous
emphysema, and so on.11-14
PAM is difficult to be diagnosed because of nonspecific symptoms in
children. The diagnosis of PAM is often based on radiographic studies at
first, and an exact diagnosis requires at least one additional clinical
feature including genetic testing demonstrating a mutation in SLC34A2,
microlith analysis, or histopathology.15 Gradually, it
has been a tendency that gene analysis would play an increasingly
important role in the diagnostic procedure. Bendstrup et al. summarized
30 genetic variants of SLC34A2 in 2020.16
In this case, we identified a PAM patient complicated with bronchitis
obliterans by computerized tomography (CT), bronchoscopy and
whole-exome-sequencing. Two novel compound heterozygous gene mutations,
gain (EXON:2-6 duplication) and c.1218C>A (p. Phe406Leu)
were identified to expand the spectrum of gene
mutations.