title: Unusual cerebrotendinous xanthomatosis with fronto-temporal dementia phenotype.
abstract: Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive lipid storage disease caused by a deficiency of the mitochondrial enzyme 27-sterol hydroxylase (CYP27). We report a 53-year-old man, with an unusual phenotype of CTX. He had xanthomas since adolescence. He had no mental retardation and developed at 44 years a progressive neuropsychiatric phenotype, suggestive of fronto-temporal dementia according to clinical Neary criteria. Cataract and ataxia were absent. Cerebral MRI revealed diffuse hyperintense T2 abnormalities in the supratentorial white matter without cerebellar atrophy or lesions, while Technetium-99m-ECD brain SPECT revealed a severe cerebellar hypoperfusion. Serum cholestanol level was elevated with excessive urinary bile alcohols excretion. Mutation analysis revealed that he was compound heterozygous for two mutations in the CYP27A1 gene: 1016 C > T (exon 5) on one allele and a novel mutation, 1435C > G (exon 8) on the other allele. A follow-up study was conducted to evaluate the effects of chenodeoxycholic acid (CDCA) and simvastatin treatment during 3 years. In spite of this treatment, cognitive functions declined but no other signs of neurological deterioration appeared.
authors.affiliation: Department of Neurology, Rouen University Hospital, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Guyant-Maréchal
authors.forename: Aad
authors.initials: A
authors.lastname: Verrips
authors.forename: Carole
authors.initials: C
authors.lastname: Girard
authors.forename: Ron A
authors.initials: RA
authors.lastname: Wevers
authors.forename: Fokje
authors.initials: F
authors.lastname: Zijlstra
authors.forename: Erik
authors.initials: E
authors.lastname: Sistermans
authors.forename: Pierre
authors.initials: P
authors.lastname: Vera
authors.forename: Dominique
authors.initials: D
authors.lastname: Campion
authors.forename: Didier
authors.initials: D
authors.lastname: Hannequin
mesh_terms: D003704:Dementia / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000523:psychology; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000523:psychology; D008875:Middle Aged; D009483:Neuropsychological Tests; D010641:Phenotype; D015899:Tomography, Emission-Computed, Single-Photon; D019294:Xanthomatosis, Cerebrotendinous / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000523:psychology