Cerebrotendinous xanthomatosis in Spain: clinical, prognostic, and genetic survey

Eur J Neurol. 2011 Oct;18(10):1203-11. doi: 10.1111/j.1468-1331.2011.03439.x. Epub 2011 Jun 4.


Background and purpose: Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disorder caused by mutations in the CYP27A1 gene resulting in sterol-27-hydroxylase deficiency. Current information about CTX is based mainly on case reports, with only few large series reported. Although perceived as a potentially treatable condition, efficacy of chenodeoxycholic acid plus statin therapy remains unclear. To perform a nationwide survey of confirmed cases, with a thorough analysis of genotype-phenotype data and prognostic factors.

Methods: Retrospective review of the clinical and epidemiological aspects and mutations of all the patients diagnosed since 1992 in the main reference centers for genetic testing of CTX in Spain.

Results: Twenty-five patients from 19 families were identified. An average delay of 19 years was observed between symptom onset and clinical diagnosis. Two main clinical subgroups were recognizable: a classic form (cerebellar and other supratentorial symptoms) and a spinal form (chronic myelopathy). Cholestanol levels did not correlate with clinical presentation, severity or response to therapy. Despite treatment, five patients died during follow-up, one to 4 years after diagnosis. Thirteen different mutations were identified, with a higher frequency of p.R395C in Northwestern Spain and p.R405W in Southern Spain. None of the mutations could be associated with a particular clinical feature combination or prognosis.

Conclusions: This is the first nationwide extensive series of CTX reported in Spain. The higher number of cases in some areas suggests a possible founder effect. Spinal forms had a less severe prognosis. A delayed diagnosis could contribute to the lack of significant response to treatment.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Female
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Male
  • Middle Aged
  • Prevalence
  • Prognosis
  • Retrospective Studies
  • Spain / epidemiology
  • Xanthomatosis, Cerebrotendinous / diagnosis*
  • Xanthomatosis, Cerebrotendinous / genetics*
  • Xanthomatosis, Cerebrotendinous / mortality
  • Young Adult