Merkens Louise S, Connor William E, Linck Leesa M, Lin Don S, Flavell Donna P, Steiner Robert D
Department of Pediatrics, Child Development and Rehabilitation Center, Doernbecher Children's Hospital, OR Health & Science University, CDRC-F, 707 SW Gaines, Portland, OR 97239, USA.
Pediatr Res. 2004 Nov;56(5):726-32. doi: 10.1203/01.PDR.0000141522.14177.4F. Epub 2004 Aug 19.
Smith-Lemli-Opitz syndrome is a condition of impaired cholesterol synthesis that is caused by mutations in DHCR7 encoding 7-dehydrocholesterol-Delta7 reductase. Birth defects and mental retardation are characteristic. Deficient plasma and tissue cholesterol and excess cholesterol precursors 7 and 8 dehydrocholesterol (7DHC and 8DHC) contribute to the pathogenesis. Cholesterol is transported to tissues via lipoproteins. We measured the effect of dietary cholesterol (egg yolk) on plasma lipoproteins to evaluate this potential treatment. We used the enzymatic method to measure total sterols in lipoproteins (n=12) and plasma (n=16). In addition, we analyzed individual plasma sterols by a gas chromatographic method. Samples were evaluated after 3 wk of a cholesterol-free diet and after 6-19 mo of dietary cholesterol. We also analyzed the distribution of sterols in lipoproteins and the apolipoprotein E genotype. Dietary cholesterol significantly increased the total sterols in plasma (2.22 +/- 0.13 to 3.10 +/- 0.22; mean +/- SEM; p < 0.002), in LDL (0.98 +/- 0.13 to 1.52 +/- 0.17 mM), and in HDL (0.72 +/- 0.04 to 0.92 +/- 0.07). Plasma cholesterol increased (1.78 +/- 0.16 to 2.67 +/- 0.25 mM; p < 0.007) and plasma 7DHC decreased in 10 children, but the mean decrease was not significant. The distribution of individual sterols in each lipoprotein fraction was similar to the distribution in plasma. The baseline cholesterol and the response to dietary cholesterol was the same in children with 3/3 and 3/4 apolipoprotein E genotypes. Dietary cholesterol increased total sterols in plasma, LDL, and HDL in children with Smith-Lemli-Opitz syndrome. These favorable increases in the lipoproteins are potentially therapeutic for this condition.
史密斯-利姆利-奥皮茨综合征是一种胆固醇合成受损的病症，由编码7-脱氢胆固醇-Δ7还原酶的DHCR7基因突变引起。出生缺陷和智力迟钝是其特征。血浆和组织胆固醇缺乏以及胆固醇前体7-脱氢胆固醇和8-脱氢胆固醇（7DHC和8DHC）过量促成了发病机制。胆固醇通过脂蛋白转运至组织。我们测量了膳食胆固醇（蛋黄）对血浆脂蛋白的影响，以评估这种潜在治疗方法。我们采用酶法测量脂蛋白（n = 12）和血浆（n = 16）中的总固醇。此外，我们通过气相色谱法分析个体血浆固醇。在无胆固醇饮食3周后以及膳食胆固醇摄入6 - 19个月后对样本进行评估。我们还分析了固醇在脂蛋白中的分布以及载脂蛋白E基因型。膳食胆固醇显著增加了血浆（从2.22±0.13至3.10±0.22；平均值±标准误；p < 0.002）、低密度脂蛋白（LDL，从0.98±0.13至1.52±0.17 mM）和高密度脂蛋白（HDL，从0.72±0.04至0.92±0.07）中的总固醇。10名儿童的血浆胆固醇升高（从1.78±0.16至2.67±0.25 mM；p < 0.007）且血浆7DHC降低，但平均降低幅度不显著。每个脂蛋白组分中个体固醇的分布与血浆中的分布相似。载脂蛋白E基因型为3/3和3/4的儿童，其基线胆固醇水平以及对膳食胆固醇的反应相同。膳食胆固醇增加了史密斯-利姆利-奥皮茨综合征患儿血浆、LDL和HDL中的总固醇。这些脂蛋白的有利增加可能对这种病症具有治疗作用。
