In 1937, Van Bogaert et al., (1937a) described a patient with cerebrotendinous xanthomatosis (CTX) and made a detailed follow-up of this man. After the patient died at the age of 40 years, a thorough postmortem study was performed. This clinicopathologic description is the most detailed ever reported for CTX. Within 3 years, two additional patients were described (Van Bogaert et al., 1937b; Epstein, 1940).
In 1968 Menkes et al. (1968) reported that there were large amounts of cholestanol in the brain of a CTX patient. Three years later, Salen (1971) found very low concentrations of chenodeoxycholic acid (CDCA) in the bile of CTX patients. In 1974 Setoguchi et al. (1974) reported a defect in bile acid synthesis. Subsequently, Salen et al. (1975) showed that CDCA therapy inhibits the synthesis of cholesterol and cholestanol in CTX patients. The deficiency of the enzyme 27-sterol hydroxylase (CYP 27) as the underlying defect in CTX, an enzyme essential in bile acid synthesis, was described by Oftebro et al. (1980). Berginer et al. (1984) confirmed the beneficial effect of CDCA as long-term therapy for CTX patients. Therapeutic β-HMG CoA reductase inhibitors were introduced, but the results were not conclusive regarding the effect of these drugs (Kuriyama et al., 1994).
Cali and Russell (1991) elucidated the sequence of cDNA of the human CYP 27 enzyme and described the first two mutations (Cali et al., 1991).