Cerebrotendinous Xanthomatosis: Molecular Pathogenesis, Clinical Spectrum, Diagnosis, and Disease-Modifying Treatments

J Atheroscler Thromb. 2021 May 8. doi: 10.5551/jat.RV17055. Online ahead of print.ABSTRACTCerebrotendinous xanthomatosis (CTX) is an autosomal recessive lipid storage disorder caused by mutations in the CYP27A1 gene, which encodes the mitochondrial enzyme sterol 27-hydroxylase. Decreased sterol 27-hydroxylase activity results in impaired bile acid synthesis, leading to reduced production of bile acids, especially chenodeoxycholic acid (CDCA), as well as elevated serum cholestanol and urine bile alcohols. The accumulation of cholestanol and cholesterol mainly in the brain, lenses, and tendons results in the characteristic clinical manifestations of CTX. Clinical presentation is characterized by systemic symptoms including neonatal jaundice or cholestasis, refractory diarrhea, juvenile cataracts, tendon xanthomas, osteoporosis, coronary heart disease, and a broad range of neuropsychiatric manifestations. The combinations of symptoms vary from patient to patient and the presenting symptoms, especially in the early disease phase, may be nonspecific, which leads to a substantial diagnostic delay or underdiagnosis. Replacement of CDCA has been approved as a first-line treatment for CTX, and can lead to biochemical and clinical improvements. However, the effect of CDCA treatment is limited once significant neuropsychiatric manifestations are established. The age at diagnosis and initiation of CDCA treatment correlate with the prognosis of patients with CTX. Therefore, early diagnosi...
Source: Journal of Atherosclerosis and Thrombosis - Category: Cardiology Authors: Source Type: research

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Source: Expert Review of Anti-Infective Therapy - Category: Infectious Diseases Tags: Expert Rev Anti Infect Ther Source Type: research
Publication date: Available online 10 October 2020Source: Journal of Vascular Surgery: Venous and Lymphatic DisordersAuthor(s): N.G. Shah, B.C. Wible, J.A. Paulisi, M. Zaki, P. Lamparello, A. Sista, M. Sadek, G.R. Jacobowitz, T.S. Maldonado
Source: Journal of Vascular Surgery: Venous and Lymphatic Disorders - Category: Surgery Source Type: research
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Source: Chemosphere - Category: Chemistry Authors: Tags: Chemosphere Source Type: research
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Source: World Journal of Hepatology - Category: Gastroenterology Tags: World J Hepatol Source Type: research
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Source: Internal Medicine - Category: Internal Medicine Tags: Intern Med Source Type: research
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Source: Internal Medicine - Category: Internal Medicine Tags: Intern Med Source Type: research
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Source: Giornale Italiano di Dermatologia e Venereologia - Category: Dermatology Tags: G Ital Dermatol Venereol Source Type: research
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Source: The Tohoku Journal of Experimental Medicine - Category: Research Authors: Tags: Tohoku J Exp Med Source Type: research
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Source: The Tohoku Journal of Experimental Medicine - Category: Research Authors: Tags: Tohoku J Exp Med Source Type: research
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Source: The Tohoku Journal of Experimental Medicine - Category: Research Authors: Tags: Tohoku J Exp Med Source Type: research
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