Elevated cholesterol precursors other than cholestanol can also be a hallmark for CTX
Elevated cholesterol precursors other than cholestanol can also be a hallmark for CTX
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DOI：
10.1007/s10545-008-0963-1
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发表时间：
2008-12-01
影响因子：
4.2
通讯作者：
Visser, G.
中科院分区：
文献类型：
--
作者：
de Sain-van der Velden, M. G. M.;Verrips, A.;Visser, G.
脑腱黄瘤病 (CTX) 是胆汁酸合成的先天性错误，其中胆固醇向胆酸和鹅去氧胆酸的肝脏转化受到损害。患者尿液中胆汁醇异常，血浆胆固醇浓度正常至升高，血浆胆甾醇浓度升高。然而，人们对 CTX 中的胆固醇前体知之甚少。我们在随访期间研究了两个患有 CTX 的兄弟姐妹的胆固醇和植物甾醇谱。虽然两名患者的胆固醇浓度都很低，但血浆胆甾醇却比对照值高出 6 倍。此外，兄弟姐妹的 7-脱氢胆固醇 (7DHC) 和 8-脱氢胆固醇 (8DHC) 含量均增加了 100 倍以上。两名患者的松甾醇、羊毛甾醇和谷甾醇均升高，而去莫甾醇和菜油甾醇浓度正常。此外，血浆黄甾醇/胆固醇比率显着升高。在接受鹅去氧胆酸盐治疗后，两名患者的胆甾醇、7DHC、8DHC、松甾醇、羊毛甾醇和谷甾醇均显着下降。此外，Lathosterol/Cholesterol 比率正常化，表明总体胆固醇合成得到充分抑制。这项研究表明，除了胆甾醇之外，胆固醇前体升高可能是 CTX 的一个标志。
Cerebrotendinous xanthomatosis (CTX) is an inborn error of bile acid synthesis in which hepatic conversion of cholesterol to cholic and chenodeoxycholic acids is impaired. Patients have abnormal bile alcohols in urine, normal to increased plasma cholesterol concentrations and increased concentrations of plasma cholestanol. Little is known about cholesterol precursors in CTX, however. We studied cholesterol and phytosterol profiles in two siblings with CTX during follow-up. While cholesterol concentrations were low in both patients, plasma cholestanol was 6-fold higher compared to control values. In addition, both siblings had a more than 100-fold increase in 7-dehydrocholesterol (7DHC) and 8-dehydrocholesterol (8DHC). Lathosterol, lanosterol and sitosterol were increased in both patients while concentrations of desmosterol and campesterol were normal. In addition, plasma lathosterol/cholesterol ratios were significantly elevated. After treatment with chenodeoxycholate, both patients showed a marked decrease in cholestanol, 7DHC, 8DHC, lathosterol, lanosterol and sitosterol. In addition, the lathosterol/cholesterol ratio normalized, indicating that overall cholesterol synthesis was sufficiently suppressed. This study shows that elevated cholesterol precursors, other than cholestanol, can be a hallmark for CTX.