title: The wide spectrum of cerebrotendinous xanthomatosis: Case report of a rare but treatable disease.
abstract: Cerebrotendinous xanthomatosis (CTX) is an autosomal-recessive disorder of lipid storage caused by mutations in the CYP27A1 gene, coding for a sterol 27-hydroxylase, leading to increased deposition of cholesterol in multiple tissues. CTX is characterized by the association of early non-neurological manifestations and adult-onset neurological dysfunctions (spastic ataxia, dementia, psychiatric disorders, peripheral neuropathy). Early and long-term treatment with chenodeoxycholic acid (CDCA) can slow down neurological symptoms progression, but diagnosis usually has a delay of several years. We report two Italian siblings having quite different phenotypes associated to a G-to-A transition in the c-1263 terminal causing a splicing alteration. This mutation has not been described before in Italy, and has been reported once in Japan. This case widens the clinical and genetic spectrum of Cerebrotendinous Xantomatosis in Italy and would like to suggest the importance of genetic testing in patients with autosomal recessive spastic paraparesis associated with typical non-neurological symptoms.
authors.affiliation: Department of Neuroscience, University of Modena and Reggio Emilia and Nuovo Ospedale Civile S. Agostino-Estense di Modena, Via Pietro Giardini n. 1355, 41126 Modena, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Rosafio
authors.affiliation: Department of Neuroscience, University of Modena and Reggio Emilia and Nuovo Ospedale Civile S. Agostino-Estense di Modena, Via Pietro Giardini n. 1355, 41126 Modena, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cavallieri
authors.affiliation: Public Local Health Authority, AUSL Modena, Nuovo ospedale di Sassuolo, Via Ruini n. 2, 41049 Sassuolo, Modena, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Guaraldi
authors.affiliation: Unit of Genetics of Neurodegenerative and Metabolic Disease, Department of Diagnostics and Applied Technology, IRCCS Foundation, C. Besta Neurological Institute, Via Celoria n. 11, 20133 Milan, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Taroni
authors.affiliation: Department of Neuroscience, University of Modena and Reggio Emilia and Nuovo Ospedale Civile S. Agostino-Estense di Modena, Via Pietro Giardini n. 1355, 41126 Modena, Italy.
authors.forename: Paolo Frigio
authors.initials: PF
authors.lastname: Nichelli
authors.affiliation: Department of Neuroscience, University of Modena and Reggio Emilia and Nuovo Ospedale Civile S. Agostino-Estense di Modena, Via Pietro Giardini n. 1355, 41126 Modena, Italy. Electronic address: j.mandrioli@ausl.mo.it.
authors.forename: Jessica
authors.initials: J
authors.lastname: Mandrioli
mesh_terms: D000328:Adult; D002635:Chenodeoxycholic Acid / Q000627:therapeutic use*; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D035583:Rare Diseases / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000235:genetics; D016896:Treatment Outcome; D019294:Xanthomatosis, Cerebrotendinous / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000235:genetics
chemical_list: D002635:Chenodeoxycholic Acid; C506831:CYP27A1 protein, human; D053493:Cholestanetriol 26-Monooxygenase
keywords: CYP27A1 gene; Cerebrotendinous xanthomatosis; Chenodeoxycholic acid; Cholesterol and cholestanol deposition; Spinocerebellar ataxia