Cerebrotendinous xanthomatosis (CTX) is a rare autosomal- recessive disorder caused by homozygous or compound heterozygous mutations in the CYP27A1 gene. These patients lack the mitochondrial sterol 27-hydroxylase enzyme, which is responsible for conversion of cholesterol to cholic acid and chenodeoxycholic acid (CDCA) in the bile synthesis pathway. CYP27A1 mutations lead to decreased synthesis of bile acids, excess production of cholestanol, and consequent accumulation of cholestanol in tissues, including brain, leading to progressive neurological dysfunction marked by dementia, spinal cord paresis, and cerebellar ataxia. Deposition in other tissues causes tendon xanthomas, premature atherosclerosis, and cataracts. The clinical manifestations usually start at infancy and develop during the first and second decades of life. The diagnosis of CTX is based on clinical findings, biochemical testing, and neuroimaging. Molecular genetic analysis although not necessary for initiation of treatment, provides definitive confirmation of CTX. Early initiation of CDCA is the treatment of choice for neurological and non-neurological symptoms of CTX and treatment with cholic acid has also been shown to be effective for non-neurological symptoms. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.
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