Clinical and biochemical aspects of primary and secondary hyperammonemic disorders
Clinical and biochemical aspects of primary and secondary hyperammonemic disorders
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DOI：
10.1016/j.abb.2013.04.009
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发表时间：
2013-08-15
影响因子：
3.9
通讯作者：
Haeberle, Johannes
中科院分区：
文献类型：
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作者：
Haeberle, Johannes
氨浓度的增加是一个非特异性的实验室迹象，表明存在通常不会被去除的潜在有毒游离氨。这确实发生在许多不同的情况下，高氨血症是替代标记物。高氨血症可能是由于氨的产生增加或解毒作用减弱而引起的，如果与临床症状相关，应视为紧急情况。根据潜在的病理生理学，可将情况分为原发性或继发性高氨血症。如果尿素循环受到任何相关酶或转运蛋白缺陷的直接影响，就会导致原发性高氨血症。然而，如果尿素循环的功能受到有毒代谢物或底物缺乏的抑制，这种情况被描述为继发性高氨血症。为了清除氨，哺乳动物除了尿素循环外，还需要谷氨酰胺合成酶的作用，以确保血氨浓度降至正常范围。无论其病因如何，如果不及早和彻底治疗，高氨血症可能会导致不可逆转的脑损伤。因此，及早认识到高氨状态并立即开始具体的管理是至关重要的。影响预后的主要因素是高氨性昏迷的持续时间和氨蓄积的程度。本文将讨论原发性和继发性高氨血症的生化背景，并概述各种潜在的情况，包括简要的临床轮廓和遗传背景的信息。(C)2013 Elsevier Inc.保留所有权利。
An increased concentration of ammonia is a non-specific laboratory sign indicating the presence of potentially toxic free ammonia that is not normally removed. This does occur in many different conditions for which hyperammonemia is a surrogate marker. Hyperammonemia can occur due to increased production or impaired detoxification of ammonia and should, if associated with clinical symptoms, be regarded as an emergency.The conditions can be classified into primary or secondary hyperammonemias depending on the underlying pathophysiology. If the urea cycle is directly affected by a defect of any of the involved enzymes or transporters, this results in primary hyperammonemia. If however the function of the urea cycle is inhibited by toxic metabolites or by substrate deficiencies, the situation is described as secondary hyperammonemia. For removal of ammonia, mammals require the action of glutamine synthetase in addition to the urea cycle, in order to ensure lowering of plasma ammonia concentrations to the normal range.Independent of its etiology, hyperammonemia may result in irreversible brain damage if not treated early and thoroughly. Thus, early recognition of a hyperammonemic state and immediate initiation of the specific management are of utmost importance. The main prognostic factors are, irrespective of the underlying cause, the duration of the hyperammonemic coma and the extent of ammonia accumulation.This paper will discuss the biochemical background of primary and secondary hyperammonemia and will give an overview of the various underlying conditions including a brief clinical outline and information on the genetic backgrounds. (C) 2013 Elsevier Inc. All rights reserved.