What is cerebrotendinous xanthomatosis (CTX)?

Updated: Jun 20, 2019
  • Author: Robert D Steiner, MD; Chief Editor: Maria Descartes, MD  more...
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Cerebrotendinous xanthomatosis (CTX) is a rare genetic metabolic disorder of cholesterol and bile acid metabolism that results in systemic and neurologic abnormalities. [1] Typically, the disease begins in infancy with chronic diarrhea. Cataracts become evident in childhood or adolescence, and xanthomata develop in the second and third decades of life. Significant neurologic impairment also occurs; this often includes seizures, dementia, and cerebellar and extrapyramidal dysfunction, typically beginning in the third decade of life and progressing until death, often in the sixth decade of life if the condition goes untreated. The presentation and course widely vary, and treatment can dramatically alter the natural history, especially with early initiation

The disease was first described in 1937 by Van Bogaert and colleagues and has since been characterized clinically, biochemically, and genetically. [2, 3] In 1968, Menkes et al described the accumulation of cholestanol, the primary metabolite found in elevated concentrations in cerebrotendinous xanthomatosis, in tissues of the CNS. [4] In 1971, Salen found that chenodeoxycholic acid (CDCA), an important bile acid, was virtually absent in patients with clinical symptoms of the disease. [5] This led to successful trials of therapy with CDCA replacement, in 1975 by Salen [6] and later with Berginer, [7] that was found to normalize the biochemical phenotype and prevent disease progression. In 1980, defects in mitochondrial sterol 27-hydroxylase were implicated in the biochemical pathophysiology of the disease by Oftebro et al. [8] In 1991, mutations in the gene CYP27A1 were discovered as causative. [9, 10, 11] Since then, more than 50 mutations have been described.

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