# Progressive respiratory failure in a term neonate with ABCA3 surfactant deficiency: Beyond the common causes of respiratory distress

## TL;DR

A term baby with ABCA3 gene mutations developed severe, treatment-resistant lung failure, highlighting the need to consider genetic causes in unexplained neonatal breathing issues.

## Contribution

This case emphasizes the importance of genetic testing for ABCA3 mutations in term infants with persistent respiratory distress.

## Key findings

- The infant had bi-allelic pathogenic variants in the ABCA3 gene, causing surfactant metabolism dysfunction.
- Standard treatments like surfactant and inhaled nitric oxide failed to improve the infant's condition.
- Lung transplantation was not an option due to the infant's size and clinical status.

## Abstract

Most cases of respiratory distress in term neonates are due to transient tachypnea of the newborn (TTN), respiratory distress syndrome (RDS), or air leak syndromes. Genetic surfactant deficiencies are rare causes of respiratory distress. Among these, mutations in the ABCA3 gene disrupt surfactant metabolism and can lead to severe, treatment-refractory respiratory failure. While commonly considered in preterm infants, surfactant dysfunction should also be considered in term infants with unexplained and persistent hypoxemia.

We present a case of a 38-weeks term female infant with fetal growth restriction who developed respiratory distress shortly after birth. She initially responded to continuous positive airway pressure (CPAP) and surfactant but required escalating respiratory support and multiple re-doses of surfactant. Standard infectious and cardiopulmonary evaluations were unrevealing. Given her persistent oxygen requirement and small-for-gestational-age status, genetic testing was pursued. Whole genome sequencing identified bi-allelic pathogenic variants in the ABCA3 gene, consistent with pulmonary surfactant metabolism dysfunction type 3. Despite six doses of surfactant, antibiotics, and inhaled nitric oxide, the patient’s respiratory status deteriorated. Lung transplantation was not feasible due to size and clinical condition. The family elected to transition to comfort care.

This case highlights the importance of considering genetic surfactant disorders, including ABCA3 mutations, in term neonates with refractory respiratory distress. Early genetic testing can guide management and avoid potentially harmful or ineffective interventions. While some therapies offer transient improvement, outcomes remain poor, and definitive treatment via lung transplantation is limited by size and disease progression. Future research should focus on gene-specific therapies and earlier diagnosis.