NUTRITION IN RETT SYNDROME

RETT 综合征的营养

• 批准号: 6241059
• 负责人: KATHLEEN J MOTIL
• 金额: $ 5.01万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-01 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6241059
• 关键词: Rett syndrome; anticonvulsants; bioenergetics; body physical activity; body weight; calcium metabolism; caloric dietary content; child (0-11); clinical research; developmental nutrition; dietary proteins; female; growth /development; hormone metabolism; hormone regulation /control mechanism; human subject; metabolism disorder; nutrition related tag; postnatal growth disorder; protein metabolism; urinalysis

Somatic growth failure is a major aspect of the developmental arrest of Rett syndrome (RS). Although reduced dietary energy intake may account for somatic growth failure, nutritional repletion does not normalize this problem. This project will examine metabolic and hormonal factors that may provide clues to the pathophysiology of somatic growth arrest in RS girls. We HYPOTHESIZE that, in the presence of positive energy balance, altered partitioning of protein and calcium balance, i.e., increased body protein degradation relative to synthesis, decreased intestinal absorption and increased urinary excretion of calcium, in the presence of reduced serum IGF-1 levels, are the mechanisms that account for persistent somatic growth failure in RS girls. The OBJECTIVE of this proposal is to identify the metabolic and/or hormonal mechanisms by which the partitioning of protein and calcium balance is altered and to estimate the contribution of these abnormalities to the protein and calcium requirements of RS girls. The SPECIFIC AIMS of this proposal are 1) to compare in RS and healthy girls: a) rates of body protein degradation, synthesis, leucine oxidation, net retention, the splanchnic extraction of lysine, and urea production; b) rates of intestinal absorption and diet- and bone-derived urinary excretion of calcium; c) insulin, IGF-1, cortisol, growth hormone, and osteocalcin levels; and 2) to determine if the abnormalities of: a) protein and calcium metabolism; b) hormone profiles, and c) somatic growth of RS girls can be reversed with dietary protein and calcium intakes in excess of recommended allowances. Two groups of SUBJECTS, RS and healthy girls, will be studied at baseline. Subsequently, RS girls will be randomized into one of two dietary protein/calcium treatment groups or a no-treatment group and studied after 1 yr. Untreated RS girls will be treated thereafter and studied a third time 1 yr. later. METHODS: Rates of body protein synthesis, degradation, net retention, and urea production will be determined using primed, constant infusions of [1-/13C] leucine, [d/4,4,5,5] lysine, and [15/N/2] urea. Rates of intestinal absorption and diet- or bone-derived urinary losses of calcium will be determine by intravenous/oral single bolus doses of 42/Ca and 46/Ca. Insulin, IGF-1, growth hormone, cortisol, and osteocalcin levels will be determined by radioimmunoassay. Body composition will be determined by 40/K counting and DEXA. Analysis of covariance without/with repeated measures will be used to determine significant differences in outcome variables between RS and healthy girls and among the high vs. usual vs. no dietary protein/calcium treatment groups. SIGNIFICANCE: The information obtained from this study will provide further insight into the metabolic and/or hormonal mechanisms that lead to somatic growth arrest in RS. A better understanding of the partitioning of dietary protein and calcium balance during conditions of altered growth will permit a more rational approach to nutritional intervention and improve the clinical outcome and quality of life of RS girls.

躯体生长障碍是发育停滞的一个主要方面。 Rett综合征(RS)。尽管饮食能量摄入的减少可能会解释 对于躯体生长障碍，营养补充并不能使其正常化 有问题。该项目将检查代谢和荷尔蒙因素， 可能为RS的躯体生长停滞的病理生理学提供线索 姑娘们。我们假设，在存在正能量平衡的情况下， 改变蛋白质和钙平衡的分配，即增加身体 蛋白质的降解与合成有关，肠道吸收减少 在尿钙减少的情况下，尿钙排泄增加 血清IGF-1水平是持续性躯体疾病的机制 RS女孩的生长发育障碍。这项提案的目标是确定 新陈代谢和/或荷尔蒙机制 蛋白质和钙的平衡被改变，并估计其贡献 这些异常对RS女孩的蛋白质和钙的需求。 这项建议的具体目的是：1)比较RS和HANDIAL 女孩：a)身体蛋白质降解、合成、亮氨酸氧化的速度， 净滞留、内脏提取赖氨酸和尿素生产； B)肠道吸收率以及饮食和骨源性尿液 钙的排泄；c)胰岛素、IGF-1、皮质醇、生长激素和 骨钙素水平；以及2)确定以下异常：a) 蛋白质和钙代谢；b)激素分布；c)体细胞生长 可以通过摄入膳食蛋白质和钙来逆转RS女孩的 超过建议的津贴。两组受试者，RS和健康人 女孩，将在基线上进行研究。随后，RS女孩将被 随机分为两个膳食蛋白质/钙处理组或 未治疗组，治疗1年后复查。未经治疗的RS女孩将被 此后接受治疗，第三次学习1年。后来。方法：RATES 体内蛋白质合成、降解、净滞留和尿素生产 将使用预置的、恒定的[1-/13C]亮氨酸输注进行测定， [D/4，4，5，5]赖氨酸和[15/N/2]尿素。肠道吸收速率和 饮食或骨源性尿钙损失将通过以下方式确定 静脉/口服单次剂量分别为42次/钙和46次/钙。胰岛素、胰岛素样生长因子-1 生长激素、皮质醇和骨钙素水平将由 放射免疫分析。身体成分将通过40/K计数来确定 和地塞米松。没有/有重复测量的协方差分析将是 用于确定RS之间结果变量的显著差异 和健康的女孩，在高饮食和正常饮食之间 蛋白质/钙处理组。意义：所获得的信息 这项研究将提供对新陈代谢和/或 导致RS躯体生长停滞的激素机制。更好的 对膳食蛋白质分配与钙平衡的认识 在变化的生长条件下，将允许一种更理性的方法 加强营养干预，提高临床疗效和质量 RS女孩的生活。