Cerebrotendinous xanthomatosis

Cerebrotendinous xanthomatosis, abbreviated CTX and also called cerebral cholesterosis, is a rare inborn disorder of bile acid metabolism caused by autosomal recessive mutations in the CYP27A1 gene. Its symptoms are wide ranging. Symptoms usually begin around the age of nineteen, with central nervous system signs first, including parkinsonism, epilepsy, dystonia, progressive ataxia, intellectual disability and dementia. Cataracts often appear in childhood, and other findings include premature atherosclerosis, osteoporosis with recurrent fractures, persistent diarrhea, gallstones and tendon xanthomas that typically develop in the second or third decade. The faulty gene lowers production of chenodeoxycholic acid and cholic acid, so cholesterol is diverted into cholestanol that accumulates in tissues. Diagnosis combines genetic analysis, imaging, biochemical tests and clinical findings, and treatment relies on bile acids, with chenodeoxycholic acid preferred, plus symptomatic care.