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.
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Acknowledgments
Work supported by grants from Ministero dell’Istruzione, dell’Università e della Ricerca-Rome (PON 2007-2013, Project BIBIOFAR) and from POR Campania FSE 2007-2013 (Project CAMPUS BIOFRAME). The authors thank Antonio Boscia, Francesco Papagni, and Concetta Sica, from University of Naples Federico II, Molecular Medicine and Medical Biotechnologies for their valuable assistance.
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Maria Donata Di Taranto and Monica Gelzo, contributed equally to this work.
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Di Taranto, M.D., Gelzo, M., Giacobbe, C. et al. Cerebrotendinous xanthomatosis, a metabolic disease with different neurological signs: two case reports. Metab Brain Dis 31, 1185–1188 (2016). https://doi.org/10.1007/s11011-016-9841-y
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DOI: https://doi.org/10.1007/s11011-016-9841-y