A New ABCA3 Gene Mutation c.3445G>A (p.Asp1149Asn) as a Causative Agent of Newborn Lethal Respiratory Distress Syndrome

• Published in: Medicina (Kaunas, Lithuania) Vol. 55; no. 7; p. 389
• Main Authors: Mitsiakos, Georgios, Tsakalidis, Christos, Karagianni, Paraskevi, Gialamprinou, Dimitra, Chatziioannidis, Ilias, Papoulidis, Ioannis, Tsanakas, Ioannis, Soubasi, Vasiliki
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 19.07.2019; MDPI AG
• Subjects: ABCA3 gene mutation; Adrenal Cortex Hormones - therapeutic use; ATP-Binding Cassette Transporters - adverse effects; ATP-Binding Cassette Transporters - genetics; Azithromycin - therapeutic use; Case Report; Humans; Hydroxychloroquine - therapeutic use; Infant, Newborn; Lung Diseases, Interstitial - genetics; Male; medical treatment; Mutation - genetics; neonatal respiratory distress syndrome; Pulmonary Surfactants - antagonists & inhibitors; Respiratory Distress Syndrome, Newborn - diagnostic imaging; Respiratory Distress Syndrome, Newborn - etiology; Respiratory Distress Syndrome, Newborn - genetics; surfactant deficiency; Tomography, X-Ray Computed - methods; surfactant deficiency; medical treatment; neonatal respiratory distress syndrome; ABCA3 gene mutation
• ISSN: 1648-9144; 1010-660X; 1648-9144; 1010-660X
• DOI: 10.3390/medicina55070389

Mutations in adenosine triphosphate-binding cassette transporter A3 (ABCA3) (OMIM: 601615) gene constitute the most frequent genetic cause of severe neonatal respiratory distress syndrome (RDS) and interstitial lung disease (ILD) in children. Interstitial lung disease in children and especially in infants, in contrast to adults, is more likely to appear as a result of developmental deficits or is characterized by genetic aberrations of pulmonary surfactant homeostasis not responding to exogenous surfactant administration. The underlying ABCA3 gene mutations are commonly thought, regarding null mutations, to determine the clinical course of the disease while there exist mutation types, especially missense variants, whose effects on surfactant proteins are difficult to predict. In addition, clinical and radiological signs overlap with those of surfactant proteins B and C mutations making diagnosis challenging. We demonstrate a case of a one-term newborn male with lethal respiratory failure caused by homozygous missense ABCA3 gene mutation c.3445G>A (p.Asp1149Asn), which, to our knowledge, was not previously reported as a causative agent of newborn lethal RDS. Therapeutic strategies for patients with ABCA3 gene mutations are not sufficiently evidence-based. Therefore, the description of the clinical course and treatment of the disease in terms of a likely correlation between genotype and phenotype is crucial for the development of the optimal clinical approach for affected individuals.