title: [Cerebrotendinous xanthomatosis: a multicentric retrospective study of 15 adults, clinical and paraclinical typical and atypical aspects].
abstract: BACKGROUND
  Cerebrotendinous xanthomatosis, a metabolic leukodystrophy with an autosomal recessive inheritance, is secondary to deficiency of sterol 27-hydroxylase, an enzyme involved in cholesterol catabolism. Classical symptoms include clinical or infraclinical xanthomas affecting the skin and tendons, early cataracts, neurological signs and diarrhea. Brain imaging reveals involvement of the dentate nuclei and periventricular white matter hyperintensities. The diagnosis is based on an increased cholestanol level in serum, confirmed by the presence of a mutation in the CYP27A1 gene. Treatment is based on chenodeoxycholic acid.
  
  
  METHODS
  We report a retrospective multicentric study of 15 cases of cerebrotendinous xanthomatosis diagnosed in French adults. Clinical, molecular and MRI findings were recorded in all patients.
  
  
  RESULTS
  The average age at diagnosis was 39years (range 27-65). Disease onset occurred in childhood in 73% of patients and in adulthood in 27%. All patients with a pediatric onset were diagnosed during adulthood (age range 28-65years). Clinical symptoms variably associated cerebellar syndrome, pyramidal syndrome, cognitive decline, epilepsy, neuropathy (sought in 10 of our patients, present in forms in 8), psychiatric disorders, cataract and xanthomas. One patient had an atypical presentation: monoparesis associated with xanthomas. Brain MRI was abnormal in all: findings consisted in T2-weighted hyperintensity of the dentate nuclei (47%), periventricular leuoencephalopathy (73%) which preferentially involved the posterior cerebral part (60%), leucoencephalopathy with a vascular pattern (7%), hyperintensity of the cortico-spinal tracts (53%), globi pallidi, corpus callosum and cerebral atrophy (33%). Serum cholestanol was elevated in 93% of patients. The most frequent mutation was 1183C>T (n=5/15). Under treatment with chenodeoxycholic acid, eight patients improved initially, followed by stabilization in five of them, and worsening in the others. Four patients died.
  
  
  CONCLUSIONS
  Patients with the xanthoma-neurological disorder association should be tested for cerebrotendinous xanthomatosis. The disease often begins in childhood with a diagnostic delay but also in adulthood. Involvement of the dentate nuclei is specific but not sensitive and the supratentorial leucoencephalopathy is not specific but with an antero-posterior gradient. A vascular distribution and involvement of the corpus callosum are possible. Serum cholestanol assay is very reliable: an elevated level provides the diagnosis, which must nevertheless be confirmed by molecular biology.
authors.affiliation: Service de neurologie, hôpital Gui-de-Chauliac, CHU de Montpellier, 80, avenue Augustin-Fliche, 34295 Montpellier, France.
authors.forename: C
authors.initials: C
authors.lastname: Lionnet
authors.affiliation: Service de neurologie, hôpital Gui-de-Chauliac, CHU de Montpellier, 80, avenue Augustin-Fliche, 34295 Montpellier, France.
authors.forename: C
authors.initials: C
authors.lastname: Carra
authors.affiliation: Service de neurologie, hôpital Gui-de-Chauliac, CHU de Montpellier, 80, avenue Augustin-Fliche, 34295 Montpellier, France.
authors.forename: X
authors.initials: X
authors.lastname: Ayrignac
authors.affiliation: Laboratoire de biochimie, hôpital Rangueil, CHU de Toulouse, 1, avenue J.-Poulhès, 31403 Toulouse, France.
authors.forename: T
authors.initials: T
authors.lastname: Levade
authors.affiliation: Service de neurologie, centre hospitalier du pays d'Aix, avenue des Tamaris, 13616 Aix-en-Provence cedex 1, France.
authors.forename: D
authors.initials: D
authors.lastname: Gayraud
authors.affiliation: Service de neurologie, hôpital Caremeau, CHU de Nîmes, place du Professeur-Debré, 30029 Nîmes cedex 4, France.
authors.forename: G
authors.initials: G
authors.lastname: Castelnovo
authors.affiliation: Service de neurologie, CHU de Grenoble, boulevard de la Chantourne, 38700 La Tronche, France.
authors.forename: G
authors.initials: G
authors.lastname: Besson
authors.affiliation: Service de neurologie, hôpital Pierre-Wertheimer, CHU de Lyon, 59, boulevard Pinel, 69500 Bron, France.
authors.forename: G
authors.initials: G
authors.lastname: Androdias
authors.affiliation: Service de neurologie, hôpital Pierre-Wertheimer, CHU de Lyon, 59, boulevard Pinel, 69500 Bron, France.
authors.forename: S
authors.initials: S
authors.lastname: Vukusic
authors.affiliation: Service de neurologie, hôpital Pierre-Wertheimer, CHU de Lyon, 59, boulevard Pinel, 69500 Bron, France.
authors.forename: C
authors.initials: C
authors.lastname: Confavreux
authors.affiliation: Cabinet privé, 64, rue Robert-Schuman, 68000 Colmar, France.
authors.forename: C
authors.initials: C
authors.lastname: Zaenker
authors.affiliation: Service de neurologie, hôpital de Hautepierre, CHU de Strasbourg, 1, avenue Molière, 67098 Strasbourg, France.
authors.forename: J
authors.initials: J
authors.lastname: De Seze
authors.affiliation: Service de neurologie, hôpital de Hautepierre, CHU de Strasbourg, 1, avenue Molière, 67098 Strasbourg, France.
authors.forename: N
authors.initials: N
authors.lastname: Collongues
authors.affiliation: Service de neurologie, hôpital de Hautepierre, CHU de Strasbourg, 1, avenue Molière, 67098 Strasbourg, France.
authors.forename: F
authors.initials: F
authors.lastname: Blanc
authors.affiliation: Service de neurologie, hôpital de Hautepierre, CHU de Strasbourg, 1, avenue Molière, 67098 Strasbourg, France.
authors.forename: C
authors.initials: C
authors.lastname: Tranchant
authors.affiliation: Service de neurologie, CHU de Rouen, 1, rue Germont, 70031 Rouen, France.
authors.forename: D
authors.initials: D
authors.lastname: Wallon
authors.affiliation: Service de neurologie, CHU de Rouen, 1, rue Germont, 70031 Rouen, France.
authors.forename: D
authors.initials: D
authors.lastname: Hannequin
authors.affiliation: Service de neurologie, hôpital Purpan, CHU de Toulouse, place du Docteur-Baylac, 31059 Toulouse cedex 9, France.
authors.forename: A
authors.initials: A
authors.lastname: Gerdelat-Mas
authors.affiliation: Service de neurologie, hôpital Purpan, CHU de Toulouse, place du Docteur-Baylac, 31059 Toulouse cedex 9, France.
authors.forename: D
authors.initials: D
authors.lastname: Brassat
authors.affiliation: Service de neurologie, hôpital Purpan, CHU de Toulouse, place du Docteur-Baylac, 31059 Toulouse cedex 9, France.
authors.forename: M
authors.initials: M
authors.lastname: Clanet
authors.affiliation: Service de neurologie D, hôpital Roger-Salengro, CHU de Lille, avenue du Pr-Émile-Laine, 59037 Lille cedex, France.
authors.forename: H
authors.initials: H
authors.lastname: Zephir
authors.affiliation: Service de neurologie D, hôpital Roger-Salengro, CHU de Lille, avenue du Pr-Émile-Laine, 59037 Lille cedex, France.
authors.forename: O
authors.initials: O
authors.lastname: Outteryck
authors.affiliation: Service de neurologie D, hôpital Roger-Salengro, CHU de Lille, avenue du Pr-Émile-Laine, 59037 Lille cedex, France.
authors.forename: P
authors.initials: P
authors.lastname: Vermersch
authors.affiliation: Service de neurologie, hôpital Gui-de-Chauliac, CHU de Montpellier, 80, avenue Augustin-Fliche, 34295 Montpellier, France. Electronic address: labauge@yahoo.fr.
authors.forename: P
authors.initials: P
authors.lastname: Labauge
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D019943:Amino Acid Substitution; D001921:Brain / Q000473:pathology; D002635:Chenodeoxycholic Acid / Q000627:therapeutic use; D053493:Cholestanetriol 26-Monooxygenase / Q000172:deficiency / Q000235:genetics; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D012189:Retrospective Studies; D063189:Symptom Assessment; D019294:Xanthomatosis, Cerebrotendinous / Q000188:drug therapy / Q000453:epidemiology / Q000473:pathology
chemical_list: D002635:Chenodeoxycholic Acid; D053493:Cholestanetriol 26-Monooxygenase
keywords: Acide chénodesoxycholique; Cataract; Cataracte; Cerebrotendinous xanthomatosis; Chenodeoxycholic acid; Cholestanol; Dentate nuclei; Leucodystrophie métabolique; Metabolic leukodystrophy; Noyaux dentelés; Xanthomas; Xanthomatose cérébrotendineuse; Xanthomes; cholestanol