Björkhem I, Leitersdorf E
Division of Clinical Chemistry, Karolinska Institutet, Huddinge University Hospital, SE-141 86 Huddinge, Sweden.
Trends Endocrinol Metab. 2000 Jul;11(5):180-3. doi: 10.1016/s1043-2760(00)00255-1.
Cerebrotendinous xanthomatosis is characterized by the accumulation of cholestanol and cholesterol in xanthomas and brain causing a number of severe symptoms. More than 20 different mutations have been identified in the gene encoding sterol 27-hydroxylase. Defects in the gene lead to reduced bile acid biosynthesis, with accumulation of 7 alpha-hydroxylated intermediates, one of which is a precursor to cholestanol. The disease can be treated successfully with chenodeoxycholic acid, which reduces the upregulation of cholesterol 7 alpha-hydroxylase and, therefore, the formation of cholestanol. Disruption of the gene encoding sterol 27-hydroxylase in mice does not have the same metabolic consequences as in humans.
脑腱黄瘤病的特征是胆固醇和胆甾烷醇在黄瘤和大脑中蓄积，从而引发多种严重症状。在编码甾醇27-羟化酶的基因中已鉴定出20多种不同的突变。该基因突变会导致胆汁酸生物合成减少，7α-羟基化中间体蓄积，其中一种是胆甾烷醇的前体。鹅去氧胆酸可成功治疗该病，它能降低胆固醇7α-羟化酶的上调，从而减少胆甾烷醇的形成。小鼠中编码甾醇27-羟化酶的基因破坏所产生的代谢后果与人类不同。
