Longitudinal Study of Urea Cycle Disorders

尿素循环障碍的纵向研究

• 批准号: 8858722
• 负责人: MARK L. BATSHAW
• 金额: $ 74.17万
• 依托单位: CHILDREN'S RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-25 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8858722
• 关键词: Adult; Amino Acids; Ammonia; Anabolism; Argininosuccinate lyase deficiency; Biochemical; Biological Markers; Blood; Carbamyl Phosphate; Characteristics; Citrullinemia; Clinical; Clinical Management; Clinical Research; Cognitive; Collection; Data; Data Collection; Defect; Development; Disease; Enzymes; European; Evidence Based Medicine; Functional disorder; Future; Glutamine; Goals; Growth; Hospitalization; Hyperammonemia; Hyperargininemia; Inborn Errors of Metabolism; Incentives; Individual; Industry Collaboration; Investigation; Investigational Drugs; Japanese Population; Kidney Diseases; Knowledge; Laboratories; Length; Liver Dysfunction; Liver diseases; Longitudinal Studies; Measures; Medical; Membrane Transport Proteins; Metabolic; Monitor; Morbidity - disease rate; N acetyl L glutamate; N-carbamylglutamate; Neurocognitive; Neurocognitive Deficit; Neurodevelopmental Deficit; Neurologic; Newborn Infant; Nitrites; Nitrogen; Ornithine carbamoyltransferase deficiency; Outcome; Pathogenesis; Patients; Pharmacotherapy; Quality of life; Rare Diseases; Research Infrastructure; Risk Factors; Role; Safety; Severities; Source; Symptoms; Syndrome; Synthase I; Time; Treatment outcome; Urea; argininosuccinate synthase; cognitive function; conventional therapy; cytokine; follow-up; improved; liver transplantation; mortality; neuroprotection; neuropsychological; novel; nutrition; ornithinemia; psychosocial; treatment center; urea cycle

Urea cycle disorders (UCD) are a group of 8 rare but devastating inborn errors of metabolism that carry a high mortality and morbidity from the newborn period through adulthood. UCD include deficiencies in any of the six enzymes and two membrane transporters involved in urea biosynthesis: N-acetylglutamate synthase deficiency (NAGSD); Carbamyl phosphate synthase I deficiency (CPSID); Ornithine transcarbamylase deficiency (OTCD); Argininosuccinate synthase deficiency (ASSD) (Citrullinemia); Argininosuccinate lyase deficiency (ASLD) (Argininosuccinic aciduria); Arginase deficiency (ARGD) (Argininemia); Hyperornithinemia, hyperammonemia, homocitrullinuria (HHH) syndrome; and Citrullinemia type 11 (CITN). The purpose of the longitudinal study project is to perform a long-term follow-up study of up to 1,100 patients with UCD. We will assess biochemical status, nutrition and cognitive function over time. We will evaluate morbidity and mortality of the most commonly used forms of treatment for UCD. We will also seek to identify biochemical parameters (biomarkers) that may predict future metabolic imbalances so that they can be corrected before clinical symptoms develop. The overall goal of this stiJdy is to improve treatment and outcome of this devastating group of disorders. Our specific aims are to; 1 Define the relationship between specific biomarkers and hyperammonemic crises; 2) Determine the long-term morbidities associated with specific UCD, especially neurocognitive deficits and hepatic and renal disease; 3) Define the outcomes of specific UCDs, including physical and neurodevelopmental deficits and their effect on quality of life; and 4) Evaluate the long-term safety and efficacy of currently used therapy for UCD (nitrogen scavengers and liver transplantation) and new and emerging treatments (N-carbamylglutamate, inorganic nitrites).

尿素循环障碍（UCD）是一组8种罕见但破坏性的先天性代谢缺陷，从新生儿期到成年期具有高死亡率和发病率。UCD包括参与尿素生物合成的六种酶和两种膜转运蛋白中任何一种的缺陷：N-乙酰谷氨酸合酶缺陷（NAGSD）;磷酸氨甲酰合酶I缺陷（CPSID）;鸟氨酸转氨甲酰酶缺陷（OTCD）;精氨酸琥珀酸合酶缺陷（ASSD）（瓜氨酸血症）;精氨基琥珀酸裂解酶缺乏症（ASLD）（精氨酸琥珀酸尿症）;精氨酸酶缺乏症（ARGD）（精氨酸血症）;高鸟氨酸血症、高氨血症、高瓜氨酸尿症（HHH）综合征;和瓜氨酸血症11型（CITN）。纵向研究项目的目的是对多达1，100名UCD患者进行长期随访研究。我们将评估生化状态，营养和认知功能随着时间的推移。我们将评估最常用的UCD治疗形式的发病率和死亡率。我们还将寻求确定可能预测未来代谢失衡的生化参数（生物标志物），以便在临床症状出现之前进行纠正。这项研究的总体目标是改善这类破坏性疾病的治疗和结局。我们的具体目标是：1确定特定生物标志物与高氨血症危象之间的关系; 2）确定与特定UCD相关的长期发病率，特别是神经认知缺陷和肝脏和肾脏疾病; 3）定义特定UCD的结局，包括身体和神经发育缺陷及其对生活质量的影响;和4）评价目前使用的UCD治疗（氮清除剂和肝移植）和新的和新兴的治疗（N-氨甲酰谷氨酸盐，无机亚硝酸盐）的长期安全性和有效性。