Cerebrotendinous Xanthomatosis (CTX)


Cerebrotendinous Xanthomatosis is caused by mutation in the CYP27A1 gene, which encodes sterol 27-hydroxylase. This enzyme catalyzes the first step in the oxidation of the side chain of sterol intermediates; the 27-hydroxylation of 5-beta-cholestane-3-alpha,7-alpha,12-alpha-triol. Cerebrotendinous Xanthomatosis is a rare, inherited lipid-storage disease with large deposits of cholesterol and cholestanol are found in virtually every tissue, particularly the Achilles tendons, brain, and lungs. Symptoms include progressive neurologic dysfunction (cerebellar ataxia beginning after puberty, systemic spinal cord involvement and a pseudobulbar phase leading to death), premature atherosclerosis, and cataracts.

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References

  1. OMIM: Entry 213700
  2. Uniprot: Q02318
  3. Engelke, U., van der Graaf, M., Heerschap, A., Hoenderop, S., Moolenaar, S., Morava, E., Wevers, R. (2007). Handbook of 1H-NMR spectroscopy in inborn errors of metabolism: body fluid NMR spectroscopy and in vivo MR spectroscopy (pp 34) (2nd ed). Heilbronn: SPS Verlagsgesellschaft
  4. Berginer VM, Abeliovich D: Genetics of cerebrotendinous xanthomatosis (CTX): an autosomal recessive trait with high gene frequency in Sephardim of Moroccan origin. Am J Med Genet. 1981;10(2):151-7. Pubmed
  5. Bjorkhem I, Fausa O, Hopen G, Oftebro H, Pedersen JI, Skrede S: Role of the 26-hydroxylase in the biosynthesis of bile acids in the normal state and in cerebrotendinous xanthomatosis. An in vivo study. J Clin Invest. 1983 Jan;71(1):142-8. Pubmed
  6. Cali JJ, Russell DW: Characterization of human sterol 27-hydroxylase. A mitochondrial cytochrome P-450 that catalyzes multiple oxidation reaction in bile acid biosynthesis. J Biol Chem. 1991 Apr 25;266(12):7774-8. Pubmed
  7. Dotti MT, Rufa A, Federico A: Cerebrotendinous xanthomatosis: heterogeneity of clinical phenotype with evidence of previously undescribed ophthalmological findings. J Inherit Metab Dis. 2001 Dec;24(7):696-706. Pubmed