UREA CYCLE ENZYMOPATHIES

尿素循环酶病

• 批准号: 3311494
• 负责人: SAUL W BRUSILOW
• 金额: $ 31.61万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-02-01 至 1986-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3311494
• 关键词: Reye's syndrome; aminoacid metabolism; arginase; arginine; argininemia; arginosuccinate lyase deficiency; arginosuccinate synthetase deficiency; benzoates; carbamoyl phosphate synthetase deficiency; carbamoylphosphate synthase; child (0-11); child psychology; citrulline; developmental nutrition; diet therapy; essential aminoacid; genetic disorder diagnosis; high performance liquid chromatography; human subject; inborn urea cycle disorder; mass screening; mental retardation; metabolism disorder chemotherapy; newborn human (0-6 weeks); nitrogen metabolism; nutrition related tag; ornithine; ornithine carbamoyl phosphate deficiency; ornithine carbamoyltransferase; patient monitoring device; phenylacetates; premature infant human; sex linked trait; urinalysis

The goal of this proposal is to develop effective methods of treating infants and children with inborn errors of ureagenesis. We propose to fulfill this goal by: 1) maintaining a national referral center to coordinate the therapeutic protocol, 2) develop a dietary nitrogen intake that will minimize the requirement for waste nitrogen excretion and activate metabolic pathways that enhance waste nitrogen excretion. These pathways include the biosynthesis and excretion of citrulline and argininosuccinic acid in argininosuccinate synthetase and lyase deficiency respectively and hippurate and phenylacetylglutamine in deficiencies of carbamyl phosphate synthetase, ornithine transcarbamylase and arginionosuccinate synthetase. 3) Improve methods of treatment of intercurrent hyperammonemic episodes by similar techniques with efforts to increase the rate of hippurate synthesis. In-vivo residual enzyme activities of patients with these diseases will be examined by studying 15NH4 enrichment of urea. This therapy will be extended to other diseases (Reye's syndrome, portalsystemic encephalopathy, organic acidemias) where hyperammonemia may have a role. It is also planned to perform a study in rats to evaluate the in vivo rate limiting steps of hippurate synthesis. The long term neurodevelopmental consequences of low grade neonatal hyperammonemia in low birth weight children will be studied by developmental and psychological methods.

该建议的目的是开发有效的治疗方法 婴儿和儿童尿素发生错误。 我们建议 实现这一目标：1）维持国家转诊中心 协调治疗方案，2）开发饮食氮摄入量 这将最大程度地减少对废物氮排泄的需求和 激活代谢途径，从而增强废物氮排泄。 这些 途径包括瓜氨酸的生物合成和排泄物 精氨酸糖酸酸中心糖酸酸合成酶和裂解酶缺乏症 分别在缺乏的缺乏症和苯乙酰谷氨酰胺 氨基甲酰磷酸合成酶，鸟氨酸经钙化酶和 精氨酸核酸合成酶。 3）改善治疗方法 通过类似技术的互动高症发作，努力 增加嬉皮士合成速率。 体内残留酶 这些疾病患者的活动将通过研究检查 15NH4释放尿素。 该疗法将扩展到其他疾病 （雷耶综合症，门遗传化脑病，有机酸血症） 高症血症可能起作用。 还计划在 大鼠评估体内速率限制速度合成的步骤。 低级新生儿的长期神经发育后果 低出生体重儿童中的高症血症将由 发展和心理方法。