Interstitial Lung Disease in a Full-term Neonate Presenting with ARDS and Hypothyroidism: A Case of an NKX 2–1-related Disorder

Case presentation

A full-term male neonate was born by spontaneous vaginal delivery at 37 weeks of gestation. Both maternal serologic tests and prenatal ultrasounds were unremarkable. Maternal vaginal-rectal swab screening for group B Streptococcus was negative. The mother was treated with L-thyroxine during pregnancy due to hypothyroidism.

The mother had rupture of membranes 26 hours before delivery but remained afebrile and received no antibiotics.

The patient had a birth weight of 3200 g and a good adaptation to extrauterine life. At 90 minutes of life, he presented with a severe acute respiratory distress syndrome (ARDS) with cyanosis, grunting, tachypnoea and retractions, and hypoxemia with peripheral oxygen saturation of 65% on room air ([Fig. 1]). Oxygen supplementation was initiated and followed by mechanical ventilation with high peak inspiratory pressure (PIP) of 37 cmH₂O and positive end expiratory pressure (PEEP) of 10 cmH₂O. The chest X-ray was compatible with grade 4 hyaline membrane versus congenital pneumonia. Intratracheal surfactant was administered with immediate but transitory improvement, and a second dose was necessary. A sepsis workup was performed, followed by intravenous administration of antibiotics (ampicillin, gentamicin, and cefotaxime). He was then referred to a tertiary hospital. Secondary transport to a paediatric intensive care unit (PICU) took place without incident.

Fig. 1 Clinical evolution during PICU stay.

On admission to the PICU, chest X-ray ([Fig. 2]) and lung ultrasound revealed bilateral hazy lung fields and a positive air bronchogram resembling congenital pneumonia. He was under mechanical ventilation with high PIP of 35–37 cmH₂O, PEEP of 10 cmH₂O and fraction of inspired oxygen (FiO2) of 0.6.

Fig. 2 a – Chest X-ray at admission in PICU. b – Lung ultrasound image before surfactant administration, showing interstitial syndrome. c – Lung ultrasound image 10 minutes after surfactant administration, revealing a normal lung scan.

At day 13, due to an elevated thyroid-stimulating hormone of 428 uIU/mL (n.v. 0.73–4.77 uIU/mL) and thyroxine of 0.4 ng/dL (n.v. 0.89–1.7 ng/dL), L-thyroxine substitution was started. The presence of maternal antithyroid antibodies was excluded. A thyroid ultrasound revealed a heterogenous tissue and small areas of liquid in the right paratracheal region.

During the stay in the PICU, repeated administrations of intratracheal surfactant and lung recruitment manoeuvres were needed due to high FiO₂ (0.75–1.0) and PIP requirements (30–35 cmH₂O), resulting in a transient improvement in oxygenation. On day 17 he was still mechanically ventilated with high settings (PIP 25 cmH₂O, PEEP 9 cmH₂O and FiO2 0.4) and despite permissive hypercapnia, it was not possible to discontinue this.

On day 28, lung ultrasound was repeated, before and after another dose of surfactant. Good improvement of the interstitial syndrome ([Fig. 2]) allowed the patient to be extubated.

The association of severe neonatal respiratory failure with the repeated need of surfactant administration and congenital hypothyroidism led to clinical suspicion of brain-lung-thyroid syndrome (BLTS).

A next-generation panel was performed and a de novo likely pathogenic NKX2–1 (NM_001079668.2) c.970dup (p.Ala324Glyfs*115) variant in heterozygosity was identified, establishing the diagnosis. The parents underwent genetic testing with normal results. No variants in the ABCA3, CSF2RA, CSF2RB, SFTPA1, SFTPB, SFTPC and SFTPD genes were found.

The patient was discharged home at 2.5 months of age under domiciliary non-invasive ventilation plus oxygen therapy, deflazacort and L-thyroxin therapy.

Currently the patient is 6 months old and maintains non-invasive ventilation during sleep plus oxygen therapy 24 hours/day and remaining therapy. Additionally, current growth and neurodevelopment are normal. Passive immunization for respiratory syncytial virus and influenza-vaccination are planned. Steroid dose reduction as well as a therapy with azithromycin and hydroxychloroquine will be considered, according to the further clinical course. He is followed up by a multidisciplinary team (endocrinology, neurology, pulmonology, and genetics).

Publikationsverlauf

Artikel online veröffentlicht:
13. September 2021