Case 1
A full-term male with unremarkable pregnancy and birth histories presented at one week of life with tachypnea and hypoxemia that progressed to respiratory failure requiring invasive mechanical ventilation with high frequency oscillatory ventilation (HFOV). Echocardiogram was unremarkable and infectious workup was negative. Chest computed tomography (CT) demonstrated patchy airspace consolidation with diffuse parenchymal ground-glass opacities (Figure 2A). Lung biopsy showed alveolar type II cell (AEC2) hyperplasia, alveolar septal fibrosis, and abundant reactive intra-alveolar macrophages. Genetic testing revealed a de novo SFTPC(NM_003018.3) pathogenic variant: c.566G>A,p.Cys189Tyr. This previously reported (2) variant affects a conserved amino acid within the BRICHOS chaperone domain, is not present in large adult genomic databases (3, 4), and is predicted damaging by in silico(5, 6).
Following diagnosis, treatment was initiated with high-dose intravenous methylprednisolone (30mg/kg IV daily for three days every month), azithromycin (5mg/kg enterally three times weekly), and hydroxychloroquine (7mg/kg enterally daily). The infant’s oxygenation improved following corticosteroid administrations, transitioning sequentially from HFOV to conventional mechanical ventilation, NIV, and ultimately nasal cannula oxygen (Figure 1A). He received feeding supplementation via nasogastric tube for 7 months, and medications at time of hospital discharge included azithromycin and hydroxychloroquine. At 8 months, supplemental oxygen was discontinued. At 2 years, chest CT showed improved parenchymal infiltrates, and enteral medications were discontinued (Figure 2B). At time of last follow-up visit, he remained nonmonic off oxygen and without significant developmental delays.