Sterol 27-hydroxylase deficiency: A rare cause of xanthomas in normocholesterolemic humans

Cerebrotendinous xanthomatosis is characterized by the accumulation of chol estanol and cholesterol in xanthomas and brain causing a number of severe s ymptoms. More than 20 different mutations have been identified in the gene encoding sterol 27-hydroxylase. Defects in the gene lead to reduced bile ac id biosynthesis, with accumulation of 7 alpha-hydroxylated intermediates, o ne of which is a precursor to cholestanol. The disease can be treated succe ssfully with chenodeoxycholic acid, which reduces the upregulation of chole sterol 7 alpha-hydroxylase and, therefore, the formation of cholestanol. Di sruption of the gene encoding sterol 27-hydroxylase in mice does not have t he same metabolic consequences as in humans.