STEROL METABOLISM & DIETARY CHOLESTEROL IN SLO SYNDROME

在Smith-Lemli-Opitz综合征（SLOS）中，血浆胆固醇水平 和组织是低的，7-脱氢胆固醇和其他 固醇含量很高。这些其他固醇是病理性的， 礼物SLOS患者阻断胆固醇的合成是因为 缺乏酶7-脱氢胆固醇δ 7-还原酶， 7-脱氢胆固醇，在胆固醇的最后一步转化为胆固醇， 胆固醇合成。主要研究者（PI）建议 膳食胆固醇来自三个不同的来源，蛋黄，晶体 胆固醇和乳脂。胆固醇吸收和 合成将在非常低胆固醇饮食和高胆固醇饮食中测定。 胆固醇饮食。使用三种不同的技术，PI将测量整体 体内胆固醇的吸收和合成以及胆汁酸的合成 SLOS患者和对照受试者。三种不同的技术包括 测定胆固醇的合成和吸收以及胆汁酸的合成 固醇平衡，通过测量 氘代水掺入红细胞胆固醇， 通过测量24小时内SLOS患者和对照受试者中甾醇合成 尿甲羟戊酸排泄。我们的目标是充分了解 7-脱氢胆固醇δ 7-还原酶缺乏对固醇代谢的影响 在SLOS。长期的饮食胆固醇补充喂养研究可能 对7-脱氢胆固醇的作用产生更明确的结果， δ 7-还原酶缺乏对甾醇代谢的影响比短期缺乏更大 补充喂养研究。一旦最佳剂量和最佳来源 膳食胆固醇（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 更长.在此期间将测量这些患者的生化参数 时间作为这些喂养研究的结果，可以设计治疗方法， 应用于SLOS患者后，立即确定他们的 条件PI的计划是识别 7-脱氢胆固醇δ 7-还原酶基因， 基于形态异常和甾醇建立基因型-表型相关性 合成.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.