Lee Sangbo, Kim Se Hee, Kim Heung Dong, Lee Joon Soo, Ko Ara, Kang Hoon-Chul
Division of Pediatric Neurology, Epilepsy Research Institute, Severance Hospital, Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea.
J Clin Neurol. 2024 Sep;20(5):519-528. doi: 10.3988/jcn.2023.0500.
Neonatal encephalopathy (NE) is a neurological syndrome that presents with severe neurological impairments and complications. Hypoxic-ischemic encephalopathy is a major contributor to poor outcomes, being responsible for 50%-80% of admissions to neonatal intensive care units. However, some cases of NE accompanied by hypoxic brain damage cannot be solely attributed to hypoxia-ischemia. We aimed to identify diverse pathogenic genetic variations that may be associated with cases of NE accompanied by hypoxic brain damage rather than hypoxia-ischemia.
We collected data from 34 patients diagnosed with NE accompanied by hypoxic brain damage over a 10-year period. Patients with the following specific conditions were excluded: 1) premature birth (<32 weeks), 2) no history of hypoxic events, 3) related anomalies, 4) neonatal infections, 5) antenatal or perinatal obstetrical complications, 6) severe hypoxia due to other medical conditions, and 7) early death (within 1 week). A comprehensive review of clinical and radiological features was conducted.
A genetic diagnosis was made in 11 (32.4%) patients, with pathogenic variants being identified in the following 9 genes: (=2), (=2), (=1), (=1), (=1), (=1), (=1), (=1), and (=1). No specific treatment outcomes or clinical features other than preterm birth were associated with the results of the genetic analyses. Personalized treatments based on the results of genetic tests were attempted, such as the administration of sodium-channel blockers in patients with or variants and the implementation of a ketogenic diet in patients with or mutations, which demonstrated some degree of effectiveness in these patients.
Genetic analyses may help in diagnosing the underlying etiology of NE and concurrent hypoxic brain damage, irrespective of the initial clinical features.
新生儿脑病（NE）是一种伴有严重神经功能障碍和并发症的神经综合征。缺氧缺血性脑病是导致不良预后的主要原因，占新生儿重症监护病房收治病例的50%-80%。然而，一些伴有缺氧性脑损伤的NE病例不能完全归因于缺氧缺血。我们旨在确定可能与伴有缺氧性脑损伤而非缺氧缺血的NE病例相关的多种致病基因变异。
我们收集了10年间34例诊断为伴有缺氧性脑损伤的NE患者的数据。排除具有以下特定情况的患者：1）早产（<32周），2）无缺氧事件病史，3）相关畸形，4）新生儿感染，5）产前或围产期产科并发症，6）因其他疾病导致的严重缺氧，7）早期死亡（1周内）。对临床和放射学特征进行了全面回顾。
11例（32.4%）患者进行了基因诊断，在以下9个基因中鉴定出致病变异：（=2），（=2），（=1），（=1），（=1），（=1），（=1），（=1），（=1）。除早产外，基因分析结果与任何特定的治疗结果或临床特征均无关联。尝试根据基因检测结果进行个性化治疗，例如对有或变异的患者给予钠通道阻滞剂，对有或突变的患者实施生酮饮食，这些治疗在这些患者中显示出一定程度的有效性。
基因分析可能有助于诊断NE及并发缺氧性脑损伤的潜在病因，而不论其初始临床特征如何。
