Cerebrotendinous xanthomatosis: clinical course, genotypes and metabolic backgrounds

Clin Invest Med. 2004 Feb;27(1):42-50.

Abstract

Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive metabolic disease. It has been reported in more than 200 people worldwide. This review covers the epidemiologic, biochemical and molecular characteristics of the disease, its clinical symptoms and treatment. A search of MEDLINE, using the keywords cerebrotendinous xanthomatosis, brain xanthoma, tendon xanthoma, cholestanol, cholesterol and bile alcohol for articles covering clinical manifestations, laboratory findings, pathology, molecular defects and treatment of CTX, revealed 175 patients with documented CTX. Of these patients, 56% were female. The incidence of tendon xanthomas was 71%, cataracts 92%, low intelligence 81% and other neurologic symptoms 100%. Several genetic studies have revealed mutations in the sterol 27-hydroxylase gene, resulting in markedly diminished activity of the enzyme in CTX patients. This genetic defect is associated with elevated plasma cholestanol levels and consequently its accumulation in the brain, lens, tendons and other tissues. The disease can be treated by the administration of chenodeoxycholic acid, a cost-effective therapy that will considerably reduce the socioeconomic burden of treating patients with CTX. The mechanism of cholestanol accumulation in affected tissues and its pathogenesis are undefined and therefore warrant further investigation.

Publication types

  • Review

MeSH terms

  • Bile Acids and Salts / metabolism
  • Cataract / complications
  • Cholestanetriol 26-Monooxygenase
  • Cholestanol / blood
  • Cholesterol / metabolism
  • Codon
  • Databases as Topic
  • Diagnosis, Differential
  • Genotype
  • Humans
  • Liver / metabolism
  • MEDLINE
  • Mutation
  • Nervous System Diseases / complications
  • Steroid Hydroxylases / genetics
  • Xanthomatosis, Cerebrotendinous / diagnosis*
  • Xanthomatosis, Cerebrotendinous / genetics*
  • Xanthomatosis, Cerebrotendinous / metabolism

Substances

  • Bile Acids and Salts
  • Codon
  • Cholestanol
  • Cholesterol
  • Steroid Hydroxylases
  • CYP27A1 protein, human
  • Cholestanetriol 26-Monooxygenase