NEUROLOGICAL DISEASES DUE TO INBORN ERRORS OF METABOLISM

先天性代谢缺陷导致的神经系统疾病

• 批准号: 8171638
• 负责人: Juan M. Pascual
• 金额: $ 1.05万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8171638
• 关键词: Affect; Aftercare; Autistic Disorder; Biopsy; Blood Tests; Brain; Carbohydrates; Child; Childhood; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; DNA; Detection; Development; Diagnosis; Disease; Epilepsy; Evaluation; Failure; Fatty acid glycerol esters; Funding; Future; Grant; Growth and Development function; Human; Image; Inborn Errors of Metabolism; Institution; Life; Magnetic Resonance Imaging; Measurement; Measures; Medical center; Mental Retardation; Metabolic; Metabolism; Methods; Mitochondria; Mitochondrial Diseases; Molecular Abnormality; Muscle; Neurologic Examination; Nuclear Magnetic Resonance; Operative Surgical Procedures; Organ; Performance; Relative (related person); Research; Research Personnel; Resources; Risk; Sampling; Source; Surrogate Markers; Techniques; Testing; Tissues; United States National Institutes of Health; base; comparison group; design; disability; human disease; improved; nervous system disorder; neurobehavioral; new technology; protein metabolism; Affect; Aftercare; Autistic Disorder; Biopsy; Blood Tests; Brain; Carbohydrates; Child; Childhood; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; DNA; Detection; Development; Diagnosis; Disease; Epilepsy; Evaluation; Failure; Fatty acid glycerol esters; Funding; Future; Grant; Growth and Development function; Human; Image; Inborn Errors of Metabolism; Institution; Life; Magnetic Resonance Imaging; Measurement; Measures; Medical center; Mental Retardation; Metabolic; Metabolism; Methods; Mitochondria; Mitochondrial Diseases; Molecular Abnormality; Muscle; Neurologic Examination; Nuclear Magnetic Resonance; Operative Surgical Procedures; Organ; Performance; Relative (related person); Research; Research Personnel; Resources; Risk; Sampling; Source; Surrogate Markers; Techniques; Testing; Tissues; United States National Institutes of Health; base; comparison group; design; disability; human disease; improved; nervous system disorder; neurobehavioral; new technology; protein metabolism

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A major challenge to understanding human metabolism is posed by the absence of methods designed to investigate living tissues and organs directly. Until now, most studies have been conducted using surrogate markers of metabolism, such as blood tests, or have utilized samples obtained through biopsies or other surgical procedures. These difficulties are compounded when repeated measurements are needed (for example, to assess changes after treatment, or to understand growth and development) or when confronted with newly recognized or poorly-understood human disease states. Many types of childhood epilepsy, mental retardation, autism and other common forms of neurobehavioral disability are now thought to be manifestation of genetic abnormalities of fat, carbohydrate and protein metabolism that affect brain development and function. Most of these diseases remain understudied and, as a consequence, treatments are necessarily unsatisfactory. We propose to combine the resources of Children's Medical Center with novel technology developed at the UT Southwestern Clements Advanced Imaging Research Center to measure metabolism in the muscles of children by NMR (nuclear magnetic resonance) techniques, the same method on which routine MRI studies are based. Children afflicted by mitochondrial diseases capable of cooperating with the performance of an MRI will be invited to participate (together with a normal comparison group) on the basis of DNA and other tests demonstrative of a mitochondrial disease and will be additionally assessed using scored physical and neurological examinations and brain MRI. We anticipate that these studies will a) help us better understand the mechanisms of mitochondrial and related energy failure diseases, b) allow us to re-define these diseases on the basis of metabolic flux and muscle content measurements, c) improve the diagnosis of these disorders, including the detection of at-risk carrier relatives, and d) identify potential quantifiable markers for the conduct and evaluation of future clinical trials.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 理解人类代谢的主要挑战是缺乏直接研究生物组织和器官的方法。到目前为止，大多数研究都是使用代谢的替代标记（例如血液检查）进行的，或者使用了通过活检或其他手术程序获得的样品。当需要重复测量时（例如，评估治疗后或了解生长和发育的变化）或面对新认识或不牢固理解的人类疾病状态时，这些困难会变得更加复杂。现在认为，许多类型的儿童癫痫，智力低下，自闭症和其他常见形式的神经行为残疾形式被认为是影响脑发育和功能的脂肪，碳水化合物和蛋白质代谢的遗传异常的表现。这些疾病中的大多数仍在研究中，因此治疗必然是不令人满意的。我们建议将儿童医疗中心的资源与在UT Southwestern Clements高级成像研究中心开发的新技术相结合，以测量NMR（核磁共振）技术在儿童肌肉中的代谢，与常规MRI研究相同的方法。通过DNA和其他证明线粒体疾病的测试，将邀请患有能够与MRI进行的线粒体疾病折磨的儿童参与（以及正常比较组），并将通过评分的物理和神经学检查以及大脑MRI进行评估。 We anticipate that these studies will a) help us better understand the mechanisms of mitochondrial and related energy failure diseases, b) allow us to re-define these diseases on the basis of metabolic flux and muscle content measurements, c) improve the diagnosis of these disorders, including the detection of at-risk carrier relatives, and d) identify potential quantifiable markers for the conduct and evaluation of future clinical trials.