defect in sterol 27-hydroxylase

A mitochondrial sterol 27-hydroxylase (CYP27A1) deficiency accounts for the development of so-called cerebrotendinous xanthomatosis (CTX). Regarding the biosynthesis of bile acids, this defect specifically interferes with the initial modifications of the cholesterol side-chain, resulting in downstream production of bile alcohols and a decreased synthesis of primary bile acids. In general, CTX must be considered a progressive lipid storage disease characterized by diarrhea (the earliest clinical manifestation, affecting approximately 75% of affected infants), cataract (appearing in the first decade of life), tendon xanthomas (adolescent- to young adult-onset), and neurologic alterations, such as dementia, psychiatric disturbances, pyramidal and/or cerebellar signs, and seizures (adult-onset). Owing to the formation of deposits of cholesterol and cholestanol, xanthomas appear on the Achilles tendon, the extensor tendons of the elbow and hand, the patellar tendon, and the neck tendons, but also in the lung, bones, and central nervous system.