title: Cerebrotendinous xanthomatosis in Spain: clinical, prognostic, and genetic survey.
abstract: OBJECTIVE
  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.
authors.affiliation: Division of Neurology, Hospital del Sureste, Ronda del Sur s/n, Arganda del Rey, Madrid, Spain. bpilodelafuente@yahoo.es
authors.forename: B
authors.initials: B
authors.lastname: Pilo-de-la-Fuente
authors.forename: A
authors.initials: A
authors.lastname: Jimenez-Escrig
authors.forename: J R
authors.initials: JR
authors.lastname: Lorenzo
authors.forename: J
authors.initials: J
authors.lastname: Pardo
authors.forename: M
authors.initials: M
authors.lastname: Arias
authors.forename: A
authors.initials: A
authors.lastname: Ares-Luque
authors.forename: J
authors.initials: J
authors.lastname: Duarte
authors.forename: S
authors.initials: S
authors.lastname: Muñiz-Pérez
authors.forename: M J
authors.initials: MJ
authors.lastname: Sobrido
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011379:Prognosis; D012189:Retrospective Studies; D013030:Spain / Q000453:epidemiology; D019294:Xanthomatosis, Cerebrotendinous / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D055815:Young Adult