N-acetylglutamate synthase deficiency: Novel mutation associated with neonatal presentation and literature review of molecular and phenotypic spectra.
N-acetylglutamate synthase deficiency: Novel mutation associated with neonatal presentation and literature review of molecular and phenotypic spectra.
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DOI：
10.1016/j.ymgmr.2016.08.004
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发表时间：
2016-09
影响因子：
1.9
通讯作者：
El-Hattab AW
中科院分区：
文献类型：
--
作者：
Al Kaabi EH;El-Hattab AW
尿素循环是处理过量氮的主要途径。氨甲酰磷酸合成酶1（carbamoyl phosphate synthetase 1，CPS 1）是尿素循环的第一个限速酶，能被N-乙酰谷氨酸（N-acetylglutamate，NAG）激活，因此N-乙酰谷氨酸合成酶（N-acetylglutamate synthetase，NAGS）是尿素循环的重要组成部分。虽然NAGS缺乏症是最罕见的尿素循环障碍，但它是唯一一种可以通过药物N-氨甲酰谷氨酸（一种激活CPS 1的NAG稳定结构类似物）特异性和有效治疗的疾病。在这里，我们报告一个婴儿与NAGS缺乏谁提出了新生儿高氨血症。她被发现有一个新的纯合剪接位点突变，c.1097-2A>T，在NAGS基因。我们描述了这个婴儿的临床过程中，谁对N-氨甲酰谷氨酸治疗反应迅速。此外，我们回顾了先前报道的NAGS缺乏症患者的临床和分子谱，大多数情况下表现为新生儿高氨血症，在某些情况下表现较晚，具有广泛的年龄和表现。由于这种广泛的迟发型表型谱，需要保持高度的怀疑指数，以早期诊断这种可治疗的疾病。
The urea cycle is the main pathway for the disposal of excess nitrogen. Carbamoylphosphate synthetase 1 (CPS1), the first and rate-limiting enzyme of urea cycle, is activated by N-acetylglutamate (NAG), and thus N-acetylglutamate synthase (NAGS) is an essential part of the urea cycle. Although NAGS deficiency is the rarest urea cycle disorder, it is the only one that can be specifically and effectively treated by a drug, N-carbamylglutamate, a stable structural analogous of NAG that activates CPS1. Here we report an infant with NAGS deficiency who presented with neonatal hyperammonemia. She was found to have a novel homozygous splice-site mutation, c.1097-2A>T, in the NAGS gene. We describe the clinical course of this infant, who had rapid response to N-carbamylglutamate treatment. In addition, we reviewed the clinical and molecular spectra of previously reported individuals with NAGS deficiency, which presents in most cases with neonatal hyperammonemia, and in some cases the presentation is later, with a broad spectrum of ages and manifestations. With this broad later-onset phenotypic spectrum, maintaining a high index of suspicion is needed for the early diagnosis of this treatable disease.