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.