Long-term treatment of girls with ornithine, transcarbamylase deficiency
Long-term treatment of girls with ornithine, transcarbamylase deficiency
复制标题
DOI：
10.1056/nejm199609193351204
复制
发表时间：
1996-09-19
影响因子：
158.5
通讯作者：
Bassett, SS
中科院分区：
文献类型：
--
作者：
Maestri, NE;Brusilow, SW;Bassett, SS
鸟氨酸转氨基甲酰基酶是一种x连锁的线粒体酶，它催化磷酸氨甲酰和鸟氨酸合成瓜氨酸。缺乏这种酶会导致高氨血症和高谷氨酰胺血症。在男孩中，如果在新生儿期发病，通常是致命的，但如果在儿童期后期发病，则病情较轻。杂合子女孩可能是正常的，也可能有高氨血症脑病发作和认知功能下降。我们在此报告了参与旨在激活废氮排泄新途径的治疗研究的鸟氨酸转氨基甲酰基酶缺乏症女孩的长期结果。方法我们研究了32例患有鸟氨酸转氨基甲酰基酶缺乏症且至少有一次脑病发作的女孩（年龄1 ~ 17岁）。患者被分配到由苯甲酸钠单独或与苯乙酸钠或苯基丁酸钠联合或单独苯基丁酸钠组成的治疗。合作医生在指定的时间间隔内提供临床、代谢和发育数据。结果根据这些方案治疗的患者5年生存率超过90%，并保持了适当的体重和身高。高氨血症发作的频率随着年龄的增长和苯乙酸钠或苯丁酸钠的治疗而降低。虽然治疗前的平均智商处于较低的平均水平，但在接受智力纵向测试的23名女孩中，有19名的测试成绩稳定。结论：有症状的鸟氨酸转氨基甲酰基酶缺乏症的女孩在接受激活废氮排泄新途径的药物治疗后，高氨血症发作次数减少，进一步认知能力下降的风险降低。(C) 1996年，马萨诸塞州医学会。
Background Ornithine transcarbamylase is an X-linked mitochondrial enzyme that catalyzes the synthesis of citrulline from carbamoyl phosphate and ornithine. A deficiency of this enzyme leads to hyperammonemia and hyperglutaminemia. In boys the disease is often fatal when its onset occurs during the neonatal period, but it is milder when onset occurs later in childhood. Heterozygous girls may be normal or may have episodes of hyperammonemic encephalopathy and decline in cognitive function. We report here on the long-term outcome in girls with ornithine transcarbamylase deficiency enrolled in studies of treatments designed to activate new pathways of waste-nitrogen excretion.Methods We studied 32 girls (age, 1 to 17 years) with ornithine transcarbamylase deficiency who had had at least one episode of encephalopathy. The patients were assigned to treatment that consisted of sodium benzoate, alone or in combination with sodium phenylacetate or sodium phenylbutyrate, or sodium phenylbutyrate alone. Collaborating physicians provided clinical, metabolic, and developmental data at specified intervals.Results Patients treated according to these protocols had greater than 90 percent survival at five years and maintained appropriate weight for height. The frequency of hyperammonemic episodes decreased with increasing age and with sodium phenylacetate or sodium phenylbutyrate treatment. Although the mean IQ before treatment was in the low average range, 19 of the 23 girls in whom intelligence was tested longitudinally had stable test scores.Conclusions Girls with symptomatic ornithine transcarbamylase deficiency who are treated with drugs that activate new pathways of waste-nitrogen excretion have fewer hyperammonemic episodes and a reduced risk of further cognitive decline. (C) 1996, Massachusetts Medical Society.