Longitudinal Study of Urea Cycle Disorders

尿素循环障碍的纵向研究

基本信息

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
项目类别：
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

项目摘要

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 种罕见但具有破坏性的先天性代谢缺陷，从新生儿期到成年期具有很高的死亡率和发病率。 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）；氨甲酰磷酸合酶 I 缺乏症 (CPSID)；鸟氨酸转氨甲酰酶缺乏症（OTCD）；精氨基琥珀酸合酶缺乏症（ASSD）（瓜氨酸血症）；精氨基琥珀酸裂解酶缺乏症（ASLD）（精氨基琥珀酸尿症）；精氨酸酶缺乏症（ARGD）（精氨酸血症）；高鸟氨酸血症、高氨血症、同型瓜氨酸尿症（HHH）综合征；和 11 型瓜氨酸血症 (CITN)。该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。我们将随着时间的推移评估生化状态、营养和认知功能。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以预测未来代谢失衡的生化参数（生物标志物），以便在出现临床症状之前对其进行纠正。本研究的总体目标是改善这一类破坏性疾病的治疗和结果。我们的具体目标是； 1 定义特定生物标志物与高氨血症危机之间的关系； 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肾疾病； 3) 定义特定UCD的结果，包括身体和神经发育缺陷及其对生活质量的影响； 4) 评估目前使用的 UCD 疗法（氮清除剂和肝移植）和新兴疗法（N-氨甲酰谷氨酸、无机亚硝酸盐）的长期安全性和有效性。