摘要
Smith-Lemli-Opitz综合征是在胆固醇合成减少的条件下形成的,这种胆固醇合成减少是由于编码的7-脱氢胆固醇-7还原酶的DHCR7基因突变引起的,其特征表现为先天性缺陷和智力发育迟滞。血浆及组织中胆固醇不足以及胆固醇前体7、8脱氢胆固醇(7DHC和8DHC)过剩是该病的病理机制。胆固醇通过脂蛋白运输到组织中,笔者测量了饮食中胆固醇(鸡蛋黄)对血浆脂蛋白的影响,以此对这种潜在的治疗方法进行评估。
Smith-Lemli-Opitz syndrome is a condition of impaired cholesterol synthesis that is caused by mutations in DHCR7 encoding 7-dehydrocholesterol- A7 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.
