Neonatal seizures (NS) occur in the first 28 days of life; they represent an important emergency that requires a rapid diagnostic work-up to start a prompt therapy. The most common causes of NS include: intraventricular haemorrhage, hypoxic-ischemic encephalopathy, hypoglycemia, electrolyte imbalance, neonatal stroke or central nervous system infection. Nevertheless, an Inborn Error of Metabolism (IEM) should be suspected in case of NS especially if these are resistant to common antiseizure drugs (ASDs) and with metabolic decompensation. Nowadays, Expanded Newborn Screening (ENS) has changed the natural history of some IEMs allowing a rapid diagnosis and a prompt onset of specific therapy; nevertheless, not all IEMs are detected by such screening (e.g. Molybdenum-Cofactor Deficiency, Hypophosphatasia, GLUT1-Deficiency Syndrome) and for this reason neonatologists have to screen for these diseases in the diagnostic work-up of NS. For IEMs, there are not specific semiology of seizures and EEG patterns. Herein, we report a systematic review on those IEMs that lead to NS and epilepsy in the neonatal period, studying only those IEMs not included in the ENS with tandem mass, suggesting clinical, biochemical features, and diagnostic work-up. Remarkably, we have observed a worse neurological outcome in infants undergoing only a treatment with common AED for their seizures, in comparison to those primarily treated with specific anti-convulsant treatment for the underlying metabolic disease (e.g.Ketogenic Diet, B6 vitamin). For this reason, we underline the importance of an early diagnosis in order to promptly intervene with a targeted treatment without waiting for drug resistance to arise.

新生儿癫痫发作 (NS) 发生在生命的最初 28 天；它们代表了一种重要的紧急情况，需要快速诊断检查才能开始及时治疗。NS 最常见的原因包括：脑室内出血、缺氧缺血性脑病、低血糖、电解质紊乱、新生儿中风或中枢神经系统感染。然而，在 NS 的情况下，应怀疑先天性代谢错误 (IEM)，特别是如果这些对常见的抗癫痫药物 (ASD) 有抗药性并伴有代谢失代偿。如今，扩大新生儿筛查 (ENS) 已经改变了一些 IEM 的自然史，可以快速诊断并迅速开始特定治疗；然而，并不是所有的 IEM 都能通过这种筛查检测到（例如钼辅因子缺乏症、低磷酸酯酶症、GLUT1-缺乏综合征），因此新生儿科医生必须在 NS 的诊断检查中筛查这些疾病。对于 IEM，没有特定的癫痫发作和 EEG 模式的符号学。在此，我们报告了对那些导致新生儿期 NS 和癫痫的 IEM 的系统评价，仅研究了那些不包括在 ENS 中的具有串联质量的 IEM，提出了临床、生化特征和诊断工作。值得注意的是，与那些主要接受针对潜在代谢疾病的特定抗惊厥治疗（例如生酮饮食、B6 维生素）的婴儿相比，我们观察到仅接受普通 AED 治疗癫痫发作的婴儿的神经系统结果更差。为此原因，