Effects of cholesterol and simvastatin treatment in patients with Smith-Lemli-Opitz syndrome (SLOS)
Effects of cholesterol and simvastatin treatment in patients with Smith-Lemli-Opitz syndrome (SLOS)
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DOI：
10.1007/s10545-007-0537-7
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发表时间：
2007-06-01
影响因子：
4.2
通讯作者：
Burgard, P.
中科院分区：
文献类型：
--
作者：
Haas, D.;Garbade, S. F.;Burgard, P.
Smith-Lemli-Opitz 综合征 (SLOS) 是由于催化胆固醇生物合成最后一步的 7-脱氢胆固醇还原酶缺乏而引起的畸形综合征。这会导致 7- 和 8- 脱氢胆固醇 (7+8-DHC) 积累，并且在大多数患者中导致胆固醇缺乏。目前的治疗包括膳食胆固醇补充剂，这会提高血浆胆固醇水平，但仅在少数患者中报告了临床效果。两项临床结果不同的小型试验显示，羟甲基戊二酰辅酶 A (HMG-CoA) 还原酶抑制剂可降低 7+8-DHC 水平并增加胆固醇浓度。这项回顾性研究评估了仅使用胆固醇和胆固醇加 HMG-CoA 还原酶抑制剂辛伐他汀对 39 名 SLOS 患者血浆甾醇和 20 名 SLOS 患者人体测量值的影响。胆固醇以及额外的辛伐他汀降低了血浆（7+8-DHC）/胆固醇比率。但导致比率下降的机制不同。这是由于仅使用胆固醇的队列中胆固醇浓度增加所致，而在接受额外辛伐他汀的队列中则证明 7+8-DHC 浓度降低。正如之前报道的那样，我们无法确认辛伐他汀治疗对人体测量或行为的积极影响。
Smith-Lemli-Opitz syndrome (SLOS) is a malformation syndrome caused by deficiency of 7-dehydrocholesterol reductase catalysing the last step of cholesterol biosynthesis. This results in an accumulation of 7- and 8-dehydrocholesterol (7+8-DHC) and, in most patients, a deficiency of cholesterol. Current therapy consists of dietary cholesterol supplementation, which raises plasma cholesterol levels, but clinical effects have been reported in only a few patients. Hydroxymethylglutaryl-coenzyme A (HMG-CoA,) reductase inhibitors were shown to reduce 7+8-DHC levels and increase cholesterol concentrations in. two small trials with divergent clinical outcome. This retrolective study evaluates the effects of cholesterol only and of cholesterol plus the HMG-CoA reductase inhibitor simvastatin on plasma sterols in 39 SLOS patients and on anthropometric measures in 20 SLOS patients. Cholesterol as well as additional simvastatin decreased the plasma (7+8-DHC)/cholesterol ratio. However, the mechanism leading to the decreasing ratio was different. Whereas it was due to an increasing cholesterol concentration in the cholesterol-only cohort, a decreasing 7+8-DHC concentration was demonstrated in the cohort receiving additional simvastatin. We could not confirm a positive effect of simvastatin treatment on anthropometric measures or behaviour, as previously reported.