PURPOSE We aimed to identify prognostic factors for survival and long-term intellectual and developmental outcome in neonatal patients with early-onset urea cycle disorders (UCD) experiencing hyperammonaemic coma. METHODS We retrospectively analysed ammonia (NH3) and glutamine levels, electroencephalogram and brain images obtained during neonatal coma of UCD patients born between 1995 and 2011 and managed at a single centre and correlated them to survival and intellectual and developmental outcome. RESULTS We included 38 neonates suffering from deficiencies of argininosuccinate synthetase (ASSD, N = 12), ornithine transcarbamylase (OTCD, N = 10), carbamoylphosphate synthetase 1 (CPSD, N = 7), argininosuccinate lyase (ASLD, N = 7), N-acetylglutamate synthase (NAGS, N = 1) or arginase (ARGD, N = 1). Symptoms occurred earlier in mitochondrial than in cytosolic UCD. Sixty-eight percent of patients survived, with a mean (standard deviation-SD) follow-up of 10.4 (5.3) years. Mortality was mostly observed in OTCD (N = 7/10) and CPSD (N = 4/7) patients. Plasma NH3 level during the neonatal period, expressed as area under the curve, but not glutamine level was associated with mortality (p = .044 and p = .610). 62.1% of the patients had normal intellectual and developmental outcome. Intellectual and developmental outcome tended to correlate with UCD subtype (p = .052). No difference in plasma NH3 or glutamine level during the neonatal period among developmental outcomes was identified. EEG severity was linked to UCD subtypes (p = .004), ammonia levels (p = .037), duration of coma (p = .043), and mortality during the neonatal period (p = .020). Status epilepticus was recorded in 6 patients, 3 of whom died neonatally, 1 developed a severe intellectual disability while the 2 last patients had a normal development. CONCLUSION UCD subtypes differed by survival rate, intellectual and developmental outcome and EEG features in the neonatal period. Hyperammonaemia expressed as area under the curve was associated with survival but not with intellectual and developmental outcome whereas glutamine was not associated with one of these outcomes. Prognostic value of video-EEG monitoring and the association between status epilepticus and mortality should be assessed in neonatal hyperammonaemic coma in further studies.

中文翻译：

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新生儿因素与早发型尿素循环障碍患者的生存以及智力和发育结局有关。

目的我们旨在确定患有高氨血症性昏迷的早发尿素循环障碍（UCD）新生儿的生存率以及长期智力和发育结局的预后因素。方法我们回顾性分析1995年至2011年间出生并在单个中心进行治疗的UCD患者新生儿昏迷期间获得的氨（NH3）和谷氨酰胺水平，脑电图和脑图像，并将其与生存率，智力和发育结局相关联。结果我们纳入了38例患有精氨琥珀酸合成酶（ASSD，N = 12），鸟氨酸转氨甲酰酶（OTCD，N = 10），氨基甲酰磷酸合成酶1（CPSD，N = 7），精氨酸琥珀酸裂合酶（ASLD，N = 7）缺陷的新生儿， N-乙酰谷氨酸合酶（NAGS，N = 1）或精氨酸酶（ARGD，N = 1）。线粒体中的症状发生早于细胞质UCD。68％的患者存活，平均随访时间（标准差-SD）为10.4（5.3）年。在OTCD（N = 7/10）和CPSD（N = 4/7）患者中，死亡率最高。新生儿时期的血浆NH3水平以曲线下面积表示，但谷氨酰胺水平与死亡率无关（p = .044和p = .610）。62.1％的患者智力和发育结局正常。智力和发育结局往往与UCD亚型相关（p = .052）。在新生儿结局之间，未发现血浆NH3或谷氨酰胺水平存在差异。脑电图的严重程度与UCD亚型（p = .004），氨水平（p = .037），昏迷持续时间（p = .043）和新生儿期的死亡率（p = .020）相关。在6例患者中记录了癫痫持续状态，其中3例新生儿死亡，其中1例患有严重的智力障碍，而最后2例患者发育正常。结论UCD亚型在新生儿期的生存率，智力和发育结局以及脑电图特征不同。曲线下面积表示的高氨血症与生存有关，但与智力和发育结果无关，而谷氨酰胺与这些结果之一无关。在进一步研究中，应在新生儿高氨血症性昏迷中评估视频脑电图监测的预后价值以及癫痫持续状态与死亡率之间的关联。结论UCD亚型在新生儿期的生存率，智力和发育结局以及脑电图特征方面存在差异。曲线下面积表示的高氨血症与生存有关，但与智力和发育结果无关，而谷氨酰胺与这些结果之一无关。在进一步研究中，应在新生儿高氨血症性昏迷中评估视频脑电图监测的预后价值以及癫痫持续状态与死亡率之间的关联。结论UCD亚型在新生儿期的生存率，智力和发育结局以及脑电图特征不同。曲线下面积表示的高氨血症与生存有关，但与智力和发育结果无关，而谷氨酰胺与这些结果之一无关。在进一步研究中，应在新生儿高氨血症性昏迷中评估视频脑电图监测的预后价值以及癫痫持续状态与死亡率之间的关联。