Koopman B J, Wolthers B G, van der Molen J C, van der Slik W, Waterreus R J, van Spreeken A
Central Laboratory for Clinical Chemistry, University Hospital, Groningen, The Netherlands.
J Inherit Metab Dis. 1988;11(1):56-75. doi: 10.1007/BF01800057.
This study gives a review of the results obtained from biochemical investigations of 20 patients in The Netherlands suffering from cerebrotendinous xanthomatosis, an inborn error of metabolism in bile acid synthesis. Diagnosis can best be established by determining the excretion of urinary bile alcohols, in particular 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha,23,25-pentol, in urine by means of capillary gas chromatography. Measurement of serum cholestanol levels or serum cholestanol/cholesterol ratios, commonly used for establishing cerebrotendinous xanthomatosis, are not reliable. The effectiveness of the different therapies, i.e. administration of bile acids, can be evaluated by monitoring the urinary excretion of bile alcohols. From such investigations it was concluded that cholic acid especially, but also chenodeoxycholic acid are the therapies of choice for the treatment of cerebrotendinous xanthomatosis. All patients, until now diagnosed in The Netherlands were not discovered before the third or fourth decade of life because the characteristic signs only then become manifest clearly. Unfortunately, because sterol storage is almost irreversible, therapy only results in minor improvements of the patient's condition. Therefore early detection of the presence of cerebrotendinous xanthomatosis is desirable so that treatment can start before extensive storage of sterols is a fact. We developed some laboratory assays with the purpose of early detection. One consists of the detection of cerebrotendinous xanthomatosis carriers by subjecting them to oral cholestyramine administration and monitoring the urinary excretion of the bile alcohol 5 beta-cholestane-3 alpha,7 alpha,12 alpha,23,25-pentol before and after treatment. Secondly, a relatively simple screening test for cerebrotendinous xanthomatosis was developed based on an enzymatic assay of 7 alpha-hydroxylated steroids in urine. After suitable modification this assay in principle allows the screening of large populations for the existence of cerebrotendinous xanthomatosis and thus to detect the disease at an earlier stage of life.
本研究综述了荷兰20例患有脑腱性黄瘤病（一种胆汁酸合成的先天性代谢缺陷疾病）患者的生化检查结果。诊断脑腱性黄瘤病的最佳方法是通过毛细管气相色谱法测定尿液中胆汁醇的排泄量，特别是5β-胆甾烷-3α,7α,12α,23,25-戊醇。常用的测定血清胆甾烷醇水平或血清胆甾烷醇/胆固醇比值来诊断脑腱性黄瘤病并不可靠。不同治疗方法（即给予胆汁酸）的疗效可通过监测胆汁醇的尿排泄量来评估。从这些研究中得出结论，尤其是胆酸，但鹅去氧胆酸也是治疗脑腱性黄瘤病的首选疗法。到目前为止，在荷兰诊断出的所有患者在生命的第三个或第四个十年之前都未被发现，因为特征性体征直到那时才明显显现出来。不幸的是，由于甾醇储存几乎是不可逆的，治疗只能使患者的病情略有改善。因此，希望能早期检测到脑腱性黄瘤病的存在，以便在甾醇大量储存之前就开始治疗。我们开发了一些实验室检测方法用于早期检测。一种方法是通过让疑似脑腱性黄瘤病携带者口服消胆胺，并监测治疗前后尿液中胆汁醇5β-胆甾烷-3α,7α,12α,23,25-戊醇的排泄量来检测携带者。其次，基于尿液中7α-羟基化甾体的酶促测定，开发了一种相对简单的脑腱性黄瘤病筛查试验。经过适当修改后，该试验原则上允许对大量人群进行脑腱性黄瘤病的筛查，从而在生命的早期阶段检测出该疾病。
