Department of Metabolic and Endocrine Diseases, University Medical Centre Utrecht, HP KC 02.069.1, Lundlaan 6 3584 CX, Utrecht, The Netherlands.
J Inherit Metab Dis. 2008 Dec;31 Suppl 2:S387-93. doi: 10.1007/s10545-008-0963-1. Epub 2008 Oct 24.
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.
脑腱黄瘤病（CTX）是一种先天性胆汁酸合成错误，肝脏将胆固醇转化为胆酸和鹅脱氧胆酸的能力受损。患者尿液中存在异常的胆汁醇，血浆胆固醇浓度正常或升高，且血浆胆甾烷醇浓度升高。然而，关于 CTX 中的胆固醇前体知之甚少。我们在 CTX 患者的随访过程中研究了两个同胞的胆固醇和植物甾醇谱。虽然两个患者的胆固醇浓度均较低，但血浆胆甾烷醇比对照值高 6 倍。此外，两个患者的 7-脱氢胆固醇（7DHC）和 8-脱氢胆固醇（8DHC）均增加了 100 多倍。两个患者的羊毛甾醇、菜油甾醇和谷甾醇均升高，而粪甾醇和菜油甾醇的浓度正常。此外，血浆羊毛甾醇/胆固醇比值显著升高。在用鹅脱氧胆酸治疗后，两个患者的胆甾烷醇、7DHC、8DHC、羊毛甾醇、菜油甾醇和谷甾醇均显著降低。此外，羊毛甾醇/胆固醇比值正常化，表明总胆固醇合成得到充分抑制。这项研究表明，升高的胆固醇前体，除胆甾烷醇外，也可能是 CTX 的一个特征。
