Stelzig Oliver, Mühlegger Beatrix, Zschocke Anna, Kiechl-Kohlendorfer Ursula, Griesmaier Elke
Department of Pediatrics II (Neonatology), Medical University of Innsbruck, Innsbruck, Austria.
Institute of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria.
BMC Pediatr. 2025 Jan 9;25(1):22. doi: 10.1186/s12887-024-05369-8.
Preterm infants are at high risk of developing respiratory distress syndrome (RDS). Mutations in the genes encoding for surfactant proteins B and C or the ATP-binding cassette transporter A3 (ABCA3) are rare but known to be associated with severe RDS and interstitial lung diseases. The exact prevalence of these mutations in the general population is difficult to determine, as they are usually studied in connection with clinical symptoms. Most cases are not captured due to variability in expression or diagnosis. It is estimated that they affect a small percentage of the population, with mutations in ABCA3 most commonly identified in association with severe lung diseases in newborns. Even heterozygous ABCA3-mutations can increase the risk and severity of RDS in neonates. The expression of these proteins is developmentally regulated, increases with gestational age, and is crucial for the function of pulmonary surfactant at birth. Additional lung stressors, such as meconium aspiration syndrome or pulmonary infections, can lead to a complex clinical picture associated with severe courses. This case report describes an extremely preterm female infant with suspected meconium aspiration syndrome, severe RDS, Mycoplasma pneumoniae infection, and a heterozygous ABCA3-mutation. The report discusses the clinical presentation, diagnostic evaluation, and therapeutic interventions, emphasizing the complexities associated with multiple pulmonary conditions in the context of extreme prematurity. At the limits of viability, therapeutic options for severe respiratory insufficiency are limited compared to older children. The developmental neurological prognosis following prolonged relative hypoxia is a crucial factor to consider in discussions about changing treatment goals. Particularly in severe cases, pulmonary infections and genetic changes in surfactant metabolism must be considered in newborns with RDS.
早产儿患呼吸窘迫综合征(RDS)的风险很高。编码表面活性蛋白B和C或ATP结合盒转运体A3(ABCA3)的基因突变很少见,但已知与严重的RDS和间质性肺病有关。这些突变在普通人群中的确切患病率难以确定,因为它们通常是结合临床症状进行研究的。由于表达或诊断的变异性,大多数病例未被发现。据估计,它们影响的人群比例很小,ABCA3突变最常与新生儿严重肺部疾病相关。即使是杂合性ABCA3突变也会增加新生儿患RDS的风险和严重程度。这些蛋白质的表达受发育调控,随胎龄增加,对出生时肺表面活性物质的功能至关重要。其他肺部应激因素,如胎粪吸入综合征或肺部感染,可导致与严重病程相关的复杂临床表现。本病例报告描述了一名极早产女婴,怀疑患有胎粪吸入综合征、严重RDS、肺炎支原体感染和杂合性ABCA3突变。报告讨论了临床表现、诊断评估和治疗干预,强调了在极早产背景下与多种肺部疾病相关的复杂性。在生存极限情况下,与大龄儿童相比,严重呼吸功能不全的治疗选择有限。在讨论改变治疗目标时,长时间相对缺氧后的发育神经学预后是一个关键因素需要考虑。特别是在严重病例中,患有RDS的新生儿必须考虑肺部感染和表面活性物质代谢的基因变化。