STEROL METABOLISM & DIETARY CHOLESTEROL IN SLO SYNDROME

Smith-Lemli-Opitz综合征(SLOS)患者血浆胆固醇水平 和组织的浓度都很低，7-脱氢胆固醇和其他 类固醇含量很高。这些其他的甾醇是病理性的，通常不是 现在时。系统性红斑狼疮患者由于 7-脱氢胆固醇三角洲7-还原酶缺乏症 7-脱氢胆固醇，在最后一步转化为胆固醇 胆固醇合成。首席调查员(PI)已提议向 饮食中的胆固醇来自三种不同的来源，蛋黄，结晶 对SLOS患者的胆固醇和乳脂。胆固醇吸收和 合成将在极低胆固醇饮食和高胆固醇饮食中被确定 胆固醇饮食。使用三种不同的技术，PI将测量整体 大鼠体内胆固醇吸收与合成及胆汁酸合成 SLOS患者和对照组。这三种不同的技术包括 测量胆固醇的合成和吸收以及胆汁酸的合成 甾醇平衡，通过测量胆固醇合成 在红细胞胆固醇中掺入氚水并测定 系统性红斑狼疮患者和正常对照组的24小时甾醇合成 尿甲丙戊酸排泄物。我们的目标是充分了解这些影响 7-脱氢胆固醇三角洲7-还原酶缺乏症对固醇代谢的影响 在SLOS中。长期膳食胆固醇补充喂养研究可能 对7-脱氢胆固醇的影响产生更明确的结果 Delta 7-还原酶缺乏症对甾醇代谢的影响 补充饲喂研究。一旦最佳剂量和最佳来源 饮食中的胆固醇(蛋黄、结晶胆固醇或乳脂) 确定后，SLOS患者的饮食将补充一年或 更久。在此期间，将测量这些患者的生化参数 时间到了。作为这些喂养研究的结果，可以设计出治疗方法，并 适用于SLOS患者在确定其 条件。这是PI的计划，以确定突变在 系统性红斑狼疮患者7-脱氢胆固醇三角洲7-还原酶基因的研究 建立基于畸形学和类固醇的基因-表型相关性 综合。将进行开发测试。

In Smith-Lemli-Opitz Syndrome (SLOS) cholesterol levels in plasma and tissue are low, and concentrations of 7-dehyrdocholesterol and other sterols are high. These other sterols are pathologic and are not normally present. Patients with SLOS block the synthesis of cholesterol because of a deficiency in enzyme 7-dehydrocholesterol delta 7-reductase, and it is 7-dehydrocholesterol that converts to cholesterol in the last step of cholesterol synthesis. The principal investigator (PI) has proposed to feed dietary cholesterol from three different sources, egg yolk, crystalline cholesterol and butterfat to SLOS patients. Cholesterol absorption and synthesis will be determined in both very low cholesterol diets and high cholesterol diets. Using three different techniques, the PI will measure whole body cholesterol absorption and synthesis as well as bile acid synthesis in SLOS patients and in control subjects. The three different techniques include measuring cholesterol synthesis and absorption and bile acid synthesis by the sterol balance, determining cholesterol synthesis by measuring the incorporation of deuterated water into erythrocyte cholesterol, and determining sterol synthesis in SLOS patients and control subjects by measuring 24-hour urinary mevalonate excretion. The objective is to fully understand the effects that 7-dehydrocholesterol delta 7-reductase deficiency has on sterol metabolism in SLOS. Long-term dietary cholesterol supplementation feeding studies might produce more definitive results about the effect that 7-dehydrocholesterol delta 7-reductase deficiency has on sterol metabolism than have short-term supplementation feeding studies. Once the optimal dose and best source of dietary cholesterol (egg yolk, crystalline cholesterol or butterfat) is determined, the diets of SLOS patients will be supplemented for one year or longer. Biochemical parameters of these patients will be measured during this time. As a result of these feeding studies, therapies can be devised and applied to SLOS patients immediately following identification of their condition. It is the PI's plan to identify mutations in the 7-dehydrocholesterol delta 7-reductase gene in SLOS patients in order to establish a genotype-phenotype correlation based on dysmorphology and sterol synthesis. Developmental testing will be performed.