Abstract：
Neonatal hypoxic-ischemic encephalopathy is a clinical phenomenon that often results from perinatal asphyxia. To mitigate secondary neurologic injury, prompt initial assessment and diagnosis is needed to identify patients eligible for therapeutic hypothermia. However, occasionally neonates present with a clinical picture of hypoxic-ischemic encephalopathy without significant risk factors for perinatal asphyxia. We hypothesized that in patients with genetic abnormalities, the clinical manifestation of those abnormalities may overlap with hypoxic-ischemic encephalopathy criteria, potentially contributing to a causal misattribution. We reviewed 210 charts of infants meeting local protocol criteria for moderate to severe hypoxic-ischemic encephalopathy in neonatal intensive care units in Calgary, Alberta. All patients that met criteria for therapeutic hypothermia were eligible for the study. Data were collected surrounding pregnancy and birth histories, as well as any available genetic or metabolic testing including microarray, gene panels, whole-exome sequencing, and newborn metabolic screens. Twenty-eight patients had genetic testing such as microarray, whole-exome sequencing, or a gene panel, because of clinical suspicion. Ten of 28 patients had genetic mutations, including CDKL5, pyruvate dehydrogenase, CFTR, CYP21A2, ISY1, KIF1A, KCNQ2, SCN9A, MTFMT, and NPHP1. All patients lacked significant risk factors to support a moderate to severe hypoxic-ischemic encephalopathy diagnosis. Treatment was changed in 2 patients because of confirmed genetic etiology. This study demonstrates the importance of identifying genetic comorbidities as potential contributors to a hypoxic-ischemic encephalopathy phenotype in neonates. Early identification of clinical factors that support an alternate diagnosis should be considered when the patient\'s clinical picture is not typical of hypoxic-ischemic encephalopathy and could aid in both treatment decisions and outcome prognostication.
摘要：
新生儿缺氧缺血性脑病是一种常引起围产期窒息的临床现象。为了减轻继发性神经损伤，需要迅速进行初步评估和诊断,以确定符合治疗性低温的患者.然而,新生儿偶尔出现缺氧缺血性脑病的临床表现，但没有围产期窒息的显著危险因素。我们假设在有基因异常的病人中,这些异常的临床表现可能与缺氧缺血性脑病标准重叠，可能导致因果错误归因。我们回顾了210张符合卡尔加里新生儿重症监护病房中度至重度缺氧缺血性脑病当地方案标准的婴儿图表，艾伯塔省.所有符合治疗性低温标准的患者均符合该研究的条件。数据收集了怀孕和出生史，以及任何可用的遗传或代谢测试，包括微阵列，基因面板，全外显子组测序,和新生儿代谢筛查。28名患者接受了基因检测，如微阵列，全外显子组测序,或者基因小组，因为临床怀疑.28个病人中有10个有基因突变,包括CDKL5，丙酮酸脱氢酶，CFTR,CYP21A2,ISY1,KIF1A,KCNQ2,SCN9A,MTFMT,NPHP1。所有患者均缺乏支持中度至重度缺氧缺血性脑病诊断的显著危险因素。2例患者因明确的遗传病因而改变治疗。这项研究证明了确定遗传合并症作为新生儿缺氧缺血性脑病表型的潜在贡献者的重要性。当患者的临床表现不典型的缺氧缺血性脑病时，应考虑早期识别支持替代诊断的临床因素，并有助于治疗决策和预后预测。
