Cerebrotendinous xanthomatosis

CYP27A1 catalyzes the side chain oxidation (27-hydroxylation) in bile acid biosynthesis. Because bile acid synthesis is the only elimination pathway for cholesterol, mutations in the CYP27A1 gene lead to abnormal deposition of cholesterol and cholestanol in various tissues. This sterol storage disorder is known as cerebrotendinous xanthomatosis. CYP27B1 is the 1-alpha hydroxylase of vitamin D3 that converts it to the active vitamin form. The function of CYP27C1 is not yet known. 

Cali JJ, Hsieh CL, Francke U, Russell DW. 1991. Mutations in the bile acid biosynthetic enzyme sterol 27-hydroxylase underlie cerebrotendinous xanthomatosis. J Biol Chem 266 7779-7783. 

Guyant-Marechal L, Verrips A, Girard C, Wevers RA, Zijlstra F, et al. 2005. Unusual cerebrotendinous xanthomatosis with fronto-temporal dementia phenotype. Am J Med Genet A 139 114-117. 

Miki H, Takeuchi H, Yamada A, Nishioka M, Matsuzawa Y, et al. 1986. Quantitative analysis of the mitochondrial cytochrome P-450-linked monooxygenase system NADPH-hepatoredoxin reductase, hepatoredoxin, and cytochrome P-450s27 in livers of patients with cerebrotendinous xanthomatosis. Clin Chim Acta 160 255-263. 

Wakamatsu N, Hayashi M, Kawai H, Kondo H, Gotoda Y, et al. 1999. Mutations producing premature termination of translation and an amino acid substitution in the sterol 27-hydroxylase gene cause cerebrotendinous xanthomatosis associated with parkinsonism. J Neurol Neurosurg Psychiatry 67 195-198. 

Defective side-chain oxidation is found in patients affected by cerebrotendinous xanthomatosis (CTX), an autosomal recessive defect characterised by deficit of mitochondrial 27-hydroxylase. The CTX defect leads to an accumulation of cholestanol and cholesterol in most tissues, while serum concentrations of CA, as well as other BAs, are sensibly low. 

Salen, G., Shefer, S., and Berginer, V. M., Familial diseases with storage of sterols other than with cholesterol Cerebrotendinous xanthomatosis and sitosterolemia with xanthomatosis. In The Metabolic Basis of Inherited Disease (J. B. Stanbury, J. B. Wyngaarden, D. S. Fredrickson, J. L. Goldstein, and M. S. Brown, eds.), 5th Ed., pp. 713-730. McGraw-Hill, New York, 1983. 

Leitersdorf, E., Meiner, V. Cerebrotendinous xanthomatosis. Curr. Opin. Lipidol. 1994 5 138-142... 

Nakamura, T., Matsuzawa, Y., Takemura, K., Knbo, M., Mikl, H., Tarui, S. Combined treatment with chenodeoxychohc acid and pravastatin improves plasma cholestanol levels associated with marked regression of tendon xanthomas in cerebrotendinous xanthomatosis. Metabolism 1991 40 741-746... 

Salen, G., Berginer, V.M., Shore, V., Horak, I., Horak, E., Tint, G.S., Shefer, S. Increased concentrations of cholestanol and apolipoprotein B in the cerebrospinal fluid of patients with cerebrotendinous xanthomatosis. New Engl. J. Med. 1987 316 1233-1238... 

Structure and Biosynthesis of Bile Alcohols Disorders of Cholesterol Side-Chain Oxidation in Cerebrotendinous Xanthomatosis... 

Isolation and Characterization of Bile Alcohols in Cerebrotendinous Xanthomatosis ( CTX1... 

Salen, G. (1971). Cholestanol deposition in cerebrotendinous xanthomatosis a possible mechanism. Ann. Intern. Med. 75 843-851. 

Menkes, J. H., Schimschok, J. R. and Swanson, P. D. (1968). Cerebrotendinous xanthomatosis The storage of cholestanol within the nervous system. Arch. Neurol. 19 47-53... 

Salen, G. and Grundy S. M. (1973). The metabolism of cholestanol, cholesterol, and bile acids in cerebrotendinous xanthomatosis. /. Clin. Invest. 52 2822-2835. 

Setoguchi, T., Salen, G., Tint, G. S. and Mosbach, E. H. (1974). A biochemical abnormality in cerebrotendinous xanthomatosis incomplete oxidation of the cholesterol side chain. J. Clin. Invest. 53 1393-1401. 

Yashuara, M., Kuramoto, T. and Hoshita, T. (1978). Identification of 5P-cholestane-3a,7a,12a,23P-tetrol, 5P-cholestane-3a,7a,12a,24a-tetrol and 5P-cholestane-3a,7a,12a,24P-tetroI in cerebrotendinous xanthomatosis. Steroids. 31 333-345. 

Dayal, B., Tint, G. S., Shefer, S., and Salen, G. (1979). Conflgurational assignment of 5P-cholestane-3a,7a,12a,23,24-pentol excreted by patients with cerebrotendinous xanthomatosis (a circular dichroism study). Steroids. 33 327-338. 

Dayal, B., Salen, G., Toome, V., and Tint, G.S. (1986). Configuration at C-25 in 5P-cholestane-3a,7a,12a,25,26-pentol excreted by patients with cerebrotendinous xanthomatosis circular dichroism and C-NMR studies. J. Lipid Res. 27 1328-1332. 

Shimazu, K., Kuwabara, M., Yoshi, M., Kihira, K., Takeuchi, H., Nakano, I., Ozawa, S., Onuki, M., Hatta, Y., and Hoshita, T. (1986). Bile alcohol profiles in bile, urine, and feces of a patient with cerebrotendinous xanthomatosis. J. Biochem. (Tokyo) 99 477-483. 

Batta, A. K., Shefer, S., Batta, M., and Salen, G. (1985). Effect of chenodeoxycholic acid on biliary and urinary bile acids and bile alcohols in cerebrotendinous xanthomatosis monitoring by high performance liquid chromatography. J. Lipid Res. 26 690-698. 

Egestad, B., Pettersson, P., Skrede, S., and Sjovall, J. (1985). Fast atom bombardment mass spectrometry in the diagnosis of cerebrotendinous xanthomatosis. Scand. J. Clin. Lab. Invest. 45 443-446. 

Oftebro, H., Bjorkhem, I., Skrede, S., Screiner, A. and Pedersen, J.I. (1980). Cerebrotendinous xanthomatosis a defect in mitochondrial 26-hydroxy lation required for normal biosynthesis of cholic acid. J. Clin. Invest.65 1418-1430. 

Berginer, V. M., Salen, G., and Shefer, S.. (1984). Long-term treatment of cerebrotendinous xanthomatosis with chenodeoxychoiic acid. Af. Engl. /.Med 311 1649-1652. 

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