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.

体细胞生长障碍是发育停滞的一个主要方面 雷特综合征（RS）。 尽管饮食能量摄入减少可能会导致 对于体细胞生长障碍，营养补充并不能使其正常化 问题。 该项目将检查代谢和激素因素 可能为RS体细胞生长停滞的病理生理学提供线索 女孩们。 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 蛋白质降解相对于合成，肠道吸收减少 并在存在减少的情况下增加尿钙排泄 血清 IGF-1 水平是导致持续性躯体疾病的机制 RS 女孩生长迟缓。 该提案的目的是确定 分配的代谢和/或激素机制 蛋白质和钙平衡发生改变并估计其贡献 这些异常影响了RS女孩对蛋白质和钙的需求。 该提案的具体目标是 1) 比较 RS 和健康 女孩：a) 身体蛋白质降解、合成、亮氨酸氧化的速率， 净保留、赖氨酸的内脏提取和尿素生产； b) 肠道吸收率以及饮食和骨源性尿的吸收率 钙的排泄； c) 胰岛素、IGF-1、皮质醇、生长激素，以及 骨钙素水平； 2) 确定是否存在以下异常： 蛋白质和钙代谢； b) 激素概况，以及 c) 体细胞生长 的 RS 女孩可以通过饮食中蛋白质和钙的摄入量来逆转 超出建议的津贴。 两组受试者，RS 组和健康组 女孩，将在基线进行研究。 随后，RS女孩将 随机分为两个膳食蛋白质/钙治疗组之一或一个 未治疗组并在 1 年后进行研究。 未经治疗的RS女孩将会 此后进行治疗并于一年内进行第三次研究。之后。 方法：费率 体内蛋白质合成、降解、净保留和尿素产生 将使用引发的、持续输注的[1-/13C]亮氨酸来确定， [d/4,4,5,5]赖氨酸和[15/N/2]尿素。 肠道吸收率和 饮食或骨源性尿钙损失将由以下因素决定 静脉/口服单次推注剂量 42/Ca 和 46/Ca。 胰岛素、IGF-1、 生长激素、皮质醇和骨钙素水平将由以下因素确定 放射免疫测定法。 身体成分将通过 40/K 计数确定 和 DEXA。 没有/有重复测量的协方差分析将是 用于确定 RS 之间结果变量的显着差异 和健康的女孩以及高饮食与正常饮食与不饮食之间的关系 蛋白质/钙治疗组。 意义：获得的信息 这项研究将提供对代谢和/或 导致 RS 体细胞生长停滞的激素机制。 更好的 了解膳食蛋白质和钙平衡的分配 在增长变化的条件下将允许采取更理性的方法 营养干预并改善临床结果和质量 RS女孩的生活。