Mathias R S, Kostiner D, Packman S
Children's Renal Center and Department of Pediatrics, Division of Medical Genetics, University of California Medical Center, San Francisco, CA 94143-0748, USA.
Am J Kidney Dis. 2001 May;37(5):1069-80. doi: 10.1016/s0272-6386(05)80026-5.
Hyperammonemia associated with inherited disorders of amino acid and organic acid metabolism is usually manifested by irritability, somnolence, vomiting, seizures, and coma. Although the majority of these patients present in the newborn period, they may also present in childhood, adolescence, and adulthood with failure to thrive, persistent vomiting, developmental delay, or behavioral changes. Persistent hyperammonemia, if not treated rapidly, may cause irreversible neuronal damage. After the diagnosis of hyperammonemia is established in an acutely ill patient, certain diagnostic tests should be performed to differentiate between urea cycle defects and other causes of hyperammonemic encephalopathy. In a patient with a presumed inherited metabolic disorder, the aim of therapy should be to normalize blood ammonia levels. Recent experience has provided treatment guidelines that include minimizing endogenous ammonia production and protein catabolism, restricting nitrogen intake, administering substrates of the urea cycle, administering compounds that facilitate the removal of ammonia through alternative pathways, and, in severe cases, dialysis therapy. Initiation of dialysis in the encephalopathic patient with hyperammonemia is indicated if the ammonia blood level is greater than three to four times the upper limit of normal. Hemodialysis is the most effective treatment for rapidly reducing blood ammonia levels. Continuous hemofiltration and peritoneal dialysis are also effective modalities for reducing blood ammonia levels. An improved understanding of the metabolism of ammonia and neurological consequences of hyperammonemia will assist the nephrologist in providing optimal care for this high-risk patient population.
与氨基酸和有机酸代谢遗传性疾病相关的高氨血症通常表现为易怒、嗜睡、呕吐、癫痫发作和昏迷。虽然这些患者大多数在新生儿期发病，但也可能在儿童期、青少年期和成年期出现，表现为生长发育迟缓、持续呕吐、发育延迟或行为改变。持续性高氨血症若不迅速治疗，可能会导致不可逆的神经元损伤。在急性病患者确诊高氨血症后，应进行某些诊断测试，以区分尿素循环缺陷和高氨血症性脑病的其他病因。对于疑似遗传性代谢紊乱的患者，治疗目标应是使血氨水平恢复正常。最近的经验提供了治疗指南，包括尽量减少内源性氨生成和蛋白质分解代谢、限制氮摄入、给予尿素循环底物、给予通过替代途径促进氨清除的化合物，以及在严重情况下进行透析治疗。如果血氨水平高于正常上限的三到四倍，则表明患有高氨血症的脑病患者需要开始透析。血液透析是迅速降低血氨水平最有效的治疗方法。持续血液滤过和腹膜透析也是降低血氨水平的有效方式。对氨代谢和高氨血症神经后果的进一步了解将有助于肾内科医生为这一高危患者群体提供最佳护理。
