Case history
A 2-year-old boy was admitted
because of intermittent fever and cough in the past 15 days. At that
time, chest computed tomography (CCT) showed bronchiectasis complicated
with extensive pneumonia in both lungs
(Fig.1 A-D). The child remained
paroxysmal irritating cough after a 10-day course of antibiotic
treatment. His father had a chronic cough caused by smoking, his mother
was in good health, and they were not consanguineous. His grandmother
was diagnosed with bronchiectasis and he had no siblings. Genetic
testing was recommended to his parents but was rejected. Thereafter, he
was lost from follow-up until he was
hospitalized at age 7 when he had been suffering a persistent cough and
expectoration for the past 2 months. He had a dry cough occasionally and
decreased exercise endurance over these past 5 years. He had not
received systematic cardiopulmonary function assessments or effective
treatments from age 2 to 7. He denied any previous history of allergies,
asthma, exposure to Mycobacterium tuberculosis oradenovirus infections. Physical examinations were unremarkable.
Blood tests showed increased white blood cell count at 17.47*10^9/L
(NE%0.76, LY%0.17, MO%0.17).
Pulmonary function tests (PFTs)
showed a restrictive syndrome with a forced vital capacity (FVC) of
1.21L (60.5% of predicted), a mild obstructive ventilation dysfunction
with a forced expiratory volume in 1 second/forced vital capacity ratio
(FEV1/FVC) of 69.8% and a positive
bronchodilation test (BDT) with
FEV1 improvement ratio at
33.6%.
CCT at age 7 (Fig.1 E-H) showed bronchiectasis, interlobular septal
thickening and lung fibrosis. And some parts showed “mosaic”
features. The mediastinal window
showed nodular calcifications in the upper and lower lobes of both lungs
(Fig.1 I-P).
Bronchoscopy showed bronchitis
obliterans (Fig.2 ) and the
Bronchoalveolar lavage fluid (BALF) was still turbid after repeating
lavage. BALF metagenomic next-generation sequence (NGS) results
suggested one positive pathogen
(Mycoplasma pneumoniae ).
The Tuberculin skin test (TST) was
medium positive (15mm). Two novel compound heterozygous mutations of the
SLC34A2 gene (Fig.3 ) were identified
by whole-exome sequencing, EXON:2-6 duplication (from the father) and
c.1218 (EXON:11) C>A (from the mother). According to the
American College of Medical Genetics
(ACMG) guidelines in 2019, 17 the biological
pathogenicity of the former was graded as “LIKELY” pathogenic, while
the latter was graded as “UNCERTAIN” significance. Based on the
evidence above, the patient was finally diagnosed with pulmonary
alveolar microlithiasis (PAM). After intravenous injection of
amoxicillin-clavulanate (600mg,
three times a day), and oral azithromycin (250mg, every other day) for a
week, his cough was partly relieved and was discharged.