PERINATOLOGY • Vol 24 • No. 1 • May–Aug 2023 • 63 Case Report Mistri J, et al. Respiratory Failure Due To a Novel Compound Heterozygous ABCA3 Mutation Introduction Pulmonary surfactant is produced by type 2 pneumocytes, and it is a complex of lipids (especially dipalmitoylphosphatidylcholine), surfactant proteins (ie, SP-A, SP-B, SP-C, and SP-D), and ATP-binding cassette subfamily A member 3 (ABCA3) protein. The pulmonary surfactant reduces surface tension at the air–liquid interface and prevents end-expiratory alveolar collapse. It is stored in lamellar bodies that are dense, multilayer secretory organelles found in type 2 pneumocytes.1 Respiratory diseases in neonatal and pediatric populations can be due to genetic mutations that disrupt the normal surfactant metabolism, which are referred to as pulmonary surfactant metabolism dysfunctions or surfactant dysfunction disorders. Respiratory failure in term neonates and interstitial lung disease (ILD) in older children and adults occur due to mutations in the SP-C, SP-D, and ABCA3, resulting in surfactant dysfunction.2 The ABCA3 gene sends a signal for the synthesis of ABCA3 protein involved in surfactant production. The ABCA3 protein is encoded by a single gene located in chromosome 16 that comprises 33 exons. The function of the ABCA3 protein is to help move phosphatidylcholine, sphingomyelin, and cholesterol to lamellar bodies.3 Though ABCA3 gene mutations appear to be the most common cause of inborn errors of surfactant metabolism, the exact incidence of these disorders is unknown. Mutations in the ABCA3 gene, associated with neonatal respiratory failure (NRF) due to surfactant deficiency and particular forms of ILD in older children, are autosomal recessive. These mutations are observed in the exons or the immediate intron–exon boundaries in most of the cases. According to a recently published article, one allele with an intronic ABCA3 mutation and another allele with a known disease-causing mutation caused NRF in a full-term neonate.4 In this case report, we discuss about a full-term male neonate with a compound heterozygous ABCA3 mutation that resulted in a fatal respiratory disease. Case Description A full-term male neonate was born through emergency cesarean section to a 31-year-old mother, in a peripheral hospital (Surendranagar, Gujarat, India), and he developed respiratory distress and grunting soon after birth. Her first male child who was born at term also had developed respiratory distress and required higher ventilatory and inotropic support immediately. The neonate’s chest radiograph was consistent with the findings of respiratory distress syndrome (RDS). The neonate eventually developed pulmonary hypertension, and he did not respond to any intervention and eventually died at 18 days of life. Genetic analysis was not done at that time. The same woman had a healthy female child in a subsequent delivery after 3 years who is presently doing well. The second male neonate (the current case) who had respiratory distress was ventilated. He required 100% FiO2; hence, he was referred to Setu Newborn Care Centre (Ahmedabad, Gujarat, India), a tertiary care center, for further management. In view of the changes observed in RDS on radiograph (Figure 1), he received a dose of surfactant to which he responded well and gradually his oxygen requirement came down over the next 48 hours. His 2D ECHO was normal. After 48 hours, his oxygen requirement started to increase and again went back to 100%. His repeat 2D ECHO suggested pulmonary hypertension, because of which he was commenced on a high-frequency oscillator, inotropic support, and pulmonary vasodilator. Blood parameters were normal, and blood culture was sterile. His chest X-ray on day 6 (Figure 2) showed features of early ILD. Due to the significant medical history of the first child, the clinical picture of the current neonate, and inconsistency in findings of RDS in the current neonate, a diagnosis of congenital surfactant deficiency was considered, and the parents were counseled for further genetic analysis. Clinical exome sequencing was requested, which showed a compound heterozygous mutation in exon 15 and exon 7 of the ABCA3 gene (Table). On day 10, the neonate remained on 100%
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