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.