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.