Alternative pathway therapy for urea cycle disorders: Twenty years later
Alternative pathway therapy for urea cycle disorders: Twenty years later
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DOI：
10.1067/mpd.2001.111836
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发表时间：
2001-01-01
影响因子：
5.1
通讯作者：
Tuchman, M
中科院分区：
文献类型：
--
作者：
Batshaw, ML;MacArthur, RB;Tuchman, M
替代途径治疗是目前公认的先天性尿素循环缺陷的治疗方法。这涉及长期使用口服苯丁酸钠、精氨酸补充剂或两者，这取决于特定的酶缺乏症，以及静脉注射苯甲酸钠/苯乙酸钠加精氨酸治疗急性高氨血症危象。回顾20年的经验，这种方法说明了这种治疗的优势和局限性。它明显降低了这些疾病的死亡率和发病率，但仍然高得令人无法接受。这些药物通常耐受性良好，但由于药物使用不频繁，已报告了严重的意外过量。新生儿和年龄较大的儿童之间的新陈代谢也存在差异，在确定剂量时必须加以解决。为了避免这些并发症，建议定期监测血液中的药物水平，并遵循非常具体的治疗方案和监督，以避免过量。最后，必须承认，替代途径治疗在预防高氨血症方面的有效性有限，必须与有效的饮食管理相结合。因此，在患有肝源性疾病或代谢控制非常差的儿童中，应考虑肝移植。还应继续寻求创新疗法，如基因疗法，以提供更持久和更彻底的矫正。
Alternative pathway therapy is currently an accepted treatment approach for inborn errors of the urea cycle. This involves the long-term use of oral sodium phenylbutyrate, arginine supplements, or both, depending on the specific enzyme deficiency, and treatment of acute hyperammonemic crises with intravenous sodium benzoate/sodium phenylacetate plus arginine. A review of 20 years of experience with this approach illustrates the strengths and limitations of this treatment. It has clearly decreased the mortality and morbidity from these disorders, but they remain unacceptably high. The medications are generally well tolerated, but severe accidental overdosage has been reported because of the infrequent use of the medication. There is also a difference in their metabolism between newborns and older children that must be addressed in determining dosage. To avoid these complications it is recommended that drug levels in blood be monitored routinely and that very specific treatment protocols and oversight be followed to avoid overdoses. Finally, it must be acknowledged that alternative pathway therapy has limited effectiveness in preventing hyperammonemia and must be combined with effective dietary management. Therefore in children with neonatal-onset disease or in those with very poor metabolic control, liver transplantation should be considered. There should also be the continued search for innovative therapies that may offer a more permanent and complete correction, such as gene therapy.