title: Cerebrotendinous xanthomatosis, a metabolic disease with different neurological signs: two case reports.
abstract: Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive inborn error of bile acids synthesis and lipid accumulation caused by a deficiency of the mitochondrial cytochrome P450 sterol 27-hydroxylase enzyme encoded by CYP27A1. Pathogenic variants in CYP27A1 cause elevated cholestanol levels in the body, which leads to a variable clinical presentation that often includes cataracts, intellectual disability, neurological features, tendon xanthomas, and chronic diarrhea. Herein we describe the cases of two unrelated adult CTX patients. Case 1 is a patient with neurological dysfunction, including moderate intellectual disability, cataract of right eye, and xanthomas; Case 2 is a patient with tendon xanthomas without neurological symptoms. Plasma sterols profile obtained from both cases showed higher levels of cholestanol and cholesterol biosynthetic precursors compared to unaffected subjects. Case 1 and Case 2 were homozygous for the c.1263 + 5G > T (p.Leu396Profs29X) and c.1435C > G (p.Arg479Gly) pathogenic variants, respectively, in the CYP27A1 gene. Interestingly, for the first time, Case 2 variant has been identified in a homozygous state. Our results highlight that the sterol profile and genetic analyses are essential to make the diagnosis of CTX and to exclude other dyslipidemias.
authors.affiliation: IRCCS Fondazione SDN, via Emanuele Gianturco 113, 80143, Naples, Italy.
authors.forename: Maria Donata
authors.initials: MD
authors.lastname: Di Taranto
authors.affiliation: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, via Sergio Pansini 5, 80131, Naples, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Gelzo
authors.affiliation: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, via Sergio Pansini 5, 80131, Naples, Italy.|CEINGE Biotecnologie Avanzate s.c. a r.l., via Gaetano Salvatore 486, 80145, Naples, Italy.
authors.forename: Carola
authors.initials: C
authors.lastname: Giacobbe
authors.affiliation: Dipartimento di Medicina Clinica e Chirurgia, Università degli Studi di Napoli Federico II, via Sergio Pansini 5, 80131, Naples, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Gentile
authors.affiliation: Dipartimento di Medicina Clinica e Chirurgia, Università degli Studi di Napoli Federico II, via Sergio Pansini 5, 80131, Naples, Italy.
authors.forename: Gennaro
authors.initials: G
authors.lastname: Marotta
authors.affiliation: Dipartimento di Medicina Clinica e Chirurgia, Università degli Studi di Napoli Federico II, via Sergio Pansini 5, 80131, Naples, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Savastano
authors.affiliation: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, via Sergio Pansini 5, 80131, Naples, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Dello Russo
authors.affiliation: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, via Sergio Pansini 5, 80131, Naples, Italy.|CEINGE Biotecnologie Avanzate s.c. a r.l., via Gaetano Salvatore 486, 80145, Naples, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Fortunato
authors.affiliation: Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi di Foggia, Viale L. Pinto 1, 71122, Foggia, Italy. gaetano.corso@unifg.it.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Corso
mesh_terms: D000328:Adult; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008659:Metabolic Diseases / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D009422:Nervous System Diseases / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D019294:Xanthomatosis, Cerebrotendinous / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*
chemical_list: C506831:CYP27A1 protein, human; D053493:Cholestanetriol 26-Monooxygenase
keywords: Bile acids synthesis disorder; Cerebrotendinous xanthomatosis; Normocholesterolemic xanthomatosis; Sterol 27-hydroxylase