A Term Neonatal Case With Lethal Respiratory Failure Associated With a Novel Homozygous Mutation in ABCA3 Gene

Abstract

The mutations in the ABCA3 (ATP-binding cassette transporter subfamily A member 3) gene could result in lethal respiratory distress syndrome (RDS) in neonates and interstitial lung disease (ILD) in infants and children. Here, we describe a full-term newborn who manifested respiratory distress 20 min after birth and then gradually developed hypoxemic respiratory failure and died on 53 days of life. A homozygous missense mutation (c.746C >T) was identified in exon 8 of ABCA3 gene in the neonate by next-generation sequencing, and the mutations were inherited from parents, respectively. This homozygous mutation is the first reported to date.

Keywords: ABCA3 gene; full-term neonate; interstitial lung diseases; lethal respiratory distress syndrome; pulmonary surfactant.

Figure 1

(A–E) The chest radiographs showed varying degrees of decreased transmittance and lung consolidation.

Figure 2

(A–D) HRCT and airway reconstruction showed decreased transmittance and ground glass opacity in bilateral lungs.

Figure 3

(A) Whole exome sequencing demonstrated a homozygous missense mutation C-to-T transition at position 746 in exon 8 of the ABCA3 gene in the neonate, which resulted in a Pro249Leu mutation. The mutations were detected in his parental DNA, respectively. (B) Protein alignment showed conservation of the P249 residue of ABCA3 across seven species.

Figure 4

The overall time curve of medication, respiratory support, arterial oxygen partial pressure, and fraction of inspire oxygen. FiO₂, fraction of inspire oxygen; PaO₂, arterial oxygen partial pressure; C, continuous positive pressure ventilation; HFO, high-frequency oscillatory ventilation; HHF, humidified high-flow oxygen; PCV, pressure controlled ventilation; Dex, dexamethasone; MP, methylprednisolone; AZM, azithromycin; PS, pulmonary surfactant.