CASE 1:
A girl weighing 2,520 g was born at 37 weeks’ gestation. The patient
developed difficulty in breathing, cough, and failure to thrive since
the age of 3 months. Her oxygen saturation was 89% in air when she was
admitted to our hospital at 4 months. Chest X-ray showed mildly
increased diffuse pulmonary infiltrates. An echocardiogram revealed
severe pulmonary hypertension and three left-to-right shunts: a small
patent ductus arteriosus (PDA), atrial and ventricular septal defect.
Chest computed tomography (CT) showed partial atelectasis in the
bilateral dorsal region and hyperinflation in the upper lobe (Figure 1a,
b). Cardiac catheterization revealed pulmonary arterial pressure of
56/28 mmHg (mean, 37 mmHg) and the ratio of the pulmonary to systemic
blood flow (Qp/Qs) was 1.1 in room air. Ambrisentan in addition to her
regular dose of sildenafil was started. At the age of 5 months, the
patient required intubation, ventilation for more than a month, and
inhaled nitric oxide due to bronchiolitis caused by respiratory
syncytial virus. Magnetic resonance imaging of the brain demonstrated
bilateral PVNH. We performed exome analysis and identified a novel
frameshift mutation c.4318delG:p.(Val1440Serfs*6) in FLNA. Sanger
sequencing confirmed it was de novo.
The patient was re-intubated and ventilated at 7 months of age due to
the sudden onset of desaturation without infection. She underwent PDA
ligation with the use of an Amplatzer Vascular Plug device because of
exacerbated pulmonary hypertension, pulmonary arterial pressure of 44/25
mmHg (mean, 34 mmHg), and Qp/Qs of 2.6. Her atrial and ventricular
septal defects were closed to reduce the risk of increased afterload.
The value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) was
6,280 pg/mL when the patient was 5 months old, which decreased to 139
pg/mL following shunt closure, and the chest radiographs improved
(Figure 1c-e). Her respiratory condition continued to improve, and she
was discharged with high-flow nasal cannula oxygen therapy at the age of
1 year.