TY - JOUR
T1 - Accumulation of 7α‐hydroxy‐4‐cholesten‐3‐one and cholesta‐4,6‐dien‐3‐one in patients with cerebrotendinous xanthomatosis
T2 - Effect of treatment with chenodeoxycholic acid
AU - Björkhem, I.
AU - Skrede, S.
AU - Buchmann, M. S.
AU - East, C.
AU - Grundy, Scott M
PY - 1987
Y1 - 1987
N2 - Evidence was recently presented that an essential part of the accumulation of cholestanol in patients with cerebrotendinous xanthomatosis is due to acceleration of a novel pathway, involving 7α‐hydroxylated intermediates in bile acid biosynthesis as precursors (J. Clin. Invest. 1985; 75:448–456). Such intermediates accumulate in patients with cerebrotendinous xanthomatosis due to lack of the mitochondrial 26‐hydroxylase involved in the major pathway for bile acid biosynthesis. The new pathway may involve the following steps: 7α‐hydroxycholesterol→7α‐hydroxy‐4‐cholesten‐3‐one→cholesta‐4,6‐dien‐3‐one→4‐cholesten‐3‐one→choles‐tanol. Accurate methods have been developed for assay of 7α‐hydroxy‐4‐cholesten‐3‐one and cholesta‐4,6‐dien‐3‐one in serum, based on isotope dilution‐mass spectrom‐etry. The serum levels of 7α‐hydroxy‐4‐cholesten‐3‐one as well as those of cholesta‐4,6‐dien‐3‐one were found to be markedly elevated in the three patients with cerebrotendinous xanthomatosis. Treatment of two of the patients with chenodeoxycholic acid reduced the serum levels of the two steroids by more than 80%. The concentration of cholestanol was reduced by 72% in one patient and by 48% in the other. The possibility is discussed that accumulation of cholestanol in patients with cerebrotendinous xanthomatosis is secondary to accumulation of 7α‐hydroxy‐4‐cho‐lesten‐3‐one and cholesta‐4,6‐dien‐3‐one.
AB - Evidence was recently presented that an essential part of the accumulation of cholestanol in patients with cerebrotendinous xanthomatosis is due to acceleration of a novel pathway, involving 7α‐hydroxylated intermediates in bile acid biosynthesis as precursors (J. Clin. Invest. 1985; 75:448–456). Such intermediates accumulate in patients with cerebrotendinous xanthomatosis due to lack of the mitochondrial 26‐hydroxylase involved in the major pathway for bile acid biosynthesis. The new pathway may involve the following steps: 7α‐hydroxycholesterol→7α‐hydroxy‐4‐cholesten‐3‐one→cholesta‐4,6‐dien‐3‐one→4‐cholesten‐3‐one→choles‐tanol. Accurate methods have been developed for assay of 7α‐hydroxy‐4‐cholesten‐3‐one and cholesta‐4,6‐dien‐3‐one in serum, based on isotope dilution‐mass spectrom‐etry. The serum levels of 7α‐hydroxy‐4‐cholesten‐3‐one as well as those of cholesta‐4,6‐dien‐3‐one were found to be markedly elevated in the three patients with cerebrotendinous xanthomatosis. Treatment of two of the patients with chenodeoxycholic acid reduced the serum levels of the two steroids by more than 80%. The concentration of cholestanol was reduced by 72% in one patient and by 48% in the other. The possibility is discussed that accumulation of cholestanol in patients with cerebrotendinous xanthomatosis is secondary to accumulation of 7α‐hydroxy‐4‐cho‐lesten‐3‐one and cholesta‐4,6‐dien‐3‐one.
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U2 - 10.1002/hep.1840070210
DO - 10.1002/hep.1840070210
M3 - Article
C2 - 3557306
AN - SCOPUS:0023221061
SN - 0270-9139
VL - 7
SP - 266
EP - 271
JO - Hepatology
JF - Hepatology
IS - 2
ER -