Cobb M M, Salen G, Tint G S, Greenspan J, Nguyen L B
Laboratory of Biochemical Genetics and Metabolism, The Rockefeller University, New York, USA.
Metabolism. 1996 Jun;45(6):673-9. doi: 10.1016/s0026-0495(96)90130-4.
Sitosterolemia is a genetic disorder characterized by sitosterol accumulation in plasma and clinically accelerated atherosclerosis. Under a condition of metabolic control with a 30% fat, low-sitosterol diet, we compared the effects of monotherapy and dual-drug treatment with lovastatin and cholestyramine on plasma sterol parameters and endogenous cholesterol synthesis in a homozygous sitosterolemic patient with concomitant heterozygous familial hypercholesterolemia (FH), her obligate heterozygous father, and hyperlipidemic control subjects. We found that for both the sitosterolemic homozygote and heterozygote, cholestyramine plus lovastatin dual therapy proved not to be superior to either drug treatment alone. In the homozygous patient, cholestyramine accounted for the decrease of plasma sterol (ie, lovastatin was ineffective), whereas in the heterozygote, lovastatin represented the margin of difference (ie, low-dose cholestyramine was relatively ineffective). Thus, the best treatment option for this homozygote child and her heterozygote father appears to be monotherapy with cholestyramine and lovastatin, respectively. Stimulation by bile acid malabsorption produced a dramatic decrease of plasma sterols in the homozygote, without increasing endogenous cholesterol synthesis, but this therapy was ineffective in the heterozygote. Decreasing endogenous cholesterol synthesis with lovastatin was effective in the heterozygote, but ineffective in the homozygote. In suspected sitosterolemia, a poor sterol response to lovastatin and a dramatic response to cholestyramine may differentiate homozygous from heterozygous and other familial forms of hyperlipidemia.
谷甾醇血症是一种遗传性疾病，其特征是血浆中谷甾醇蓄积，临床上表现为动脉粥样硬化加速。在采用30%脂肪、低谷甾醇饮食进行代谢控制的条件下，我们比较了洛伐他汀和考来烯胺单药治疗及联合用药对一名患有纯合子谷甾醇血症并伴有杂合子家族性高胆固醇血症（FH）的患者、其必然杂合子父亲以及高脂血症对照受试者血浆甾醇参数和内源性胆固醇合成的影响。我们发现，对于谷甾醇血症纯合子和杂合子而言，考来烯胺加洛伐他汀联合治疗并不优于单独使用任何一种药物治疗。在纯合子患者中，考来烯胺导致血浆甾醇降低（即洛伐他汀无效），而在杂合子中，洛伐他汀显示出差异（即低剂量考来烯胺相对无效）。因此，对于这名纯合子儿童及其杂合子父亲而言，最佳治疗方案似乎分别是考来烯胺和洛伐他汀单药治疗。胆汁酸吸收不良刺激导致纯合子血浆甾醇显著降低，且未增加内源性胆固醇合成，但该疗法在杂合子中无效。用洛伐他汀降低内源性胆固醇合成在杂合子中有效，但在纯合子中无效。在疑似谷甾醇血症中，对洛伐他汀的甾醇反应不佳以及对考来烯胺的显著反应可能有助于区分纯合子与杂合子以及其他家族性高脂血症形式。
