Cholestanol

General Information

Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive neurologic disease characterized by xanthomas of tendons, lungs, and the brain despite normal or low plasma cholesterol concentrations. Other major clinical manifestations include diarrhea, cataracts, premature atherosclerosis and myocardial infarction, progressive cerebellar ataxia, dementia, spinal cord paresis, and belownormal intelligence. Greatly increased concentrations of cholestanol, the 5a-dihydro derivative of cholesterol, in plasma and in practically all tissues, notably xanthoma, nerve tissues, and brain, have been reported.

Small amounts of cholestanol normally accompany cholesterol in virtually every mammalian tissue. The major metabolic defect in the CTX syndrome is the impaired synthesis of chenodeoxycholic acid from cholesterol. There is a deficiency of the mitochondrial sterol 27-hydroxylase enzyme, which catalyzes the initial steps in the oxidation of the side chain of the cholesterol structure in the conversion of cholesterol to bile acids. The CTX syndrome has been traced to a mutation of the sterol 27 hydroxylase (CYP27A1) gene on chromosome 2q33-qter. Several other mutations of the sterol 27-hydroxylase gene have now been reported. It has been suggested that the accumulation of cholestanol in the tissues is secondary to this mutation of the CYP27A1 gene.
From Bhattacharyya et al. Journal of Lipid Research Volume 48, P.185-192, 2007