Review
Neurosciences
Rodrigo Mariano Ribeiro, Sophia Costa Vasconcelos, Pedro Lucas Grangeiro de Sa Barreto Lima, Emanuel Ferreira Coelho, Anna Melissa Noronha Oliveira, Emanuel de Assis Bertulino Martins Gomes, Luciano de Albuquerque Mota, Lucas Soares Radtke, Matheus dos Santos Carvalho, David Augusto Batista Sa Araujo, Maria Suelly Nogueira Pinheiro, Vitor Carneiro de Vasconcelos Gama, Renan Magalhaes Montenegro Junior, Pedro Braga Neto, Paulo Ribeiro Nobrega
Summary: Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive disorder caused by CYP27A1 gene mutations, resulting in sterol 27-hydroxylase deficiency. This leads to the accumulation of cholesterol and other lipids in various tissues. Lipid profile evaluations of CTX patients consistently show elevated levels of cholestanol and normal or low serum cholesterol levels. Decreased chenodeoxycholic acid (CDCA) levels lead to increased synthesis of cholesterol metabolites, such as bile alcohols, which can serve as markers in CTX patients. Lipid abnormalities in CTX have clinical implications, contributing to neurological symptoms, tendon xanthomas, and increased risk of atherosclerosis and cardiovascular complications.
Review
Peripheral Vascular Disease
Shingo Koyama, Yoshiki Sekijima, Masatsune Ogura, Mika Hori, Kota Matsuki, Takashi Miida, Mariko Harada-Shiba
Summary: Cerebrotendinous xanthomatosis (CTX) is a rare genetic disorder characterized by a variety of systemic symptoms including jaundice, diarrhea, cataracts, tendon xanthomas, osteoporosis, coronary heart disease, and neuropsychiatric manifestations. Early diagnosis and treatment initiation are crucial for the prognosis of CTX patients.
JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS
(2021)
Article
Clinical Neurology
Shingo Koyama, Yuma Okabe, Yuya Suzuki, Ryosuke Igari, Hiroyasu Sato, Chifumi Iseki, Kazuyo Tanji, Kyoko Suzuki, Yasuyuki Ohta
Summary: CTX is a lipid storage disorder caused by mutations in the CYP27A1 gene, leading to different clinical phenotypes and treatment responses. Early diagnosis and treatment are crucial for improving long-term outcomes.
Article
Pharmacology & Pharmacy
Christos Stenos, Konstantinos Kalafatakis, Pantelis Constantoulakis, Katerina Zekiou, Anna Margoni, Panagiota Kardara, Aspasia Terentiou, Georgios Stouraitis, Georgios Nikolaou
Summary: Cerebrotendinous xanthomatosis (CTX) is a rare inherited disorder caused by mutations in the CYP27A1 gene, leading to deficiencies in bile acid biosynthesis and resulting in the accumulation of sterol 27-hydroxylase in the central nervous system and tendons. This disorder presents with a variety of systemic symptoms and clinical heterogeneity, making prompt diagnosis challenging. This case report highlights the importance of maintaining a high index of suspicion for CTX, as early diagnosis and treatment can lead to significant improvements in symptoms.
JOURNAL OF CLINICAL LIPIDOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Petar Brlek, Luka Bulic, David Glavas Weinberger, Jelena Bosnjak, Tomislav Pavlovic, Svetlana Tomic, Zdravka Krivdic Dupan, Igor Boric, Dragan Primorac
Summary: Cerebrotendinous xanthomatosis (CTX) is a genetic disorder that affects the cholesterol metabolic pathway. It is caused by variants in the CYP27A1 gene and leads to the accumulation of cholestanol in neuronal tissue and tendons. Treatment with chenodeoxycholic acid (CDCA) can be effective in halting the production of these metabolites.
Review
Biochemistry & Molecular Biology
Andrea E. DeBarber, P. Barton Duell
Summary: Cerebrotendinous xanthomatosis (CTX) is a rare genetic disorder with highly variable clinical presentation. Early diagnosis and treatment are crucial for better outcomes. New diagnostic algorithms, screening strategies, and improved biochemical testing contribute to enhanced diagnosis and evaluation of treatment efficacy.
CURRENT OPINION IN LIPIDOLOGY
(2021)
Article
Clinical Neurology
Monica Gelzo, Maria Donata Di Taranto, Alvino Bisecco, Alessandra D'Amico, Rocco Capuano, Carola Giacobbe, Mafalda Caputo, Mario Cirillo, Gioacchino Tedeschi, Giuliana Fortunato, Gaetano Corso
Summary: CTX is a rare genetic metabolic disorder caused by a defect in bile acid biosynthesis, characterized by chronic diarrhea, cataracts, xanthomas, and neurological dysfunction, with significant variability in symptoms and age of onset. Early diagnosis through biochemical and genetic screening is crucial for timely pharmacological intervention and prevention of neurological complications.
ACTA NEUROLOGICA BELGICA
(2021)
Article
Endocrinology & Metabolism
Pelin Teke Kisa, Gonca Kilic Yildirim, Burcu Ozturk Hismi, Sevil Dorum, Ozge Yilmaz Kusbeci, Ali Topak, Figen Baydan, Fatma Nazli Durmaz Celik, Orhan Gorukmez, Zumrut Arslan Gulten, Arzu Ekici, Serhat Ozkan, Aylin Yaman, Nur Arslan
Summary: Cerebrotendinous xanthomatosis (CTX) is a lipid storage disease caused by deficiency of sterol 27-hydroxylase enzyme. Clinical presentation varies between children and adults, with early diagnosis crucial in children. Treatment with chenodeoxycholic acid can improve symptoms, but pediatric patients tend to have lower Mignarri scores.
METABOLIC BRAIN DISEASE
(2021)
Article
Pharmacology & Pharmacy
Natalja Bouwhuis, Bart A. W. Jacobs, E. Marleen Kemper
Summary: This study demonstrates the development of CDCA capsules as a viable alternative for Dutch patients with CTX due to the unavailability of the drug in 2017. The pharmacy preparations were found to be of high quality and compliance with GMP requirements through product validation and stability studies.
FRONTIERS IN PHARMACOLOGY
(2023)
Editorial Material
Endocrinology & Metabolism
Sarah Marie Brike, Wouter Meersseman, David Cassiman
Summary: Profit-driven games resulted in discontinuation of proper treatment for a patient with cerebrotendinous xanthomatosis, leading to disastrous consequences for his health.
JOURNAL OF INHERITED METABOLIC DISEASE
(2022)
Review
Clinical Neurology
Paulo Ribeiro Nobrega, Anderson Moura Bernardes, Rodrigo Mariano Ribeiro, Sophia Costa Vasconcelos, David Augusto Batista Sa Araujo, Vitor Carneiro de Vasconcelos Gama, Helena Fussiger, Carolina de Figueiredo Santos, Daniel Aguiar Dias, Andre Luiz Santos Pessoa, Wladimir Bocca Vieira de Rezende Pinto, Jonas Alex Morales Saute, Paulo Victor Sgobbi de Souza, Pedro Braga-Neto
Summary: Cerebrotendinous Xanthomatosis is a rare and underdiagnosed neurometabolic disorder with diverse neurological presentations. Treatment with chenodeoxycholic acid has shown effectiveness, but its availability and cost limit its use.
FRONTIERS IN NEUROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jun-Jun Lee, Chiung-Chih Chang, Wen-Neng Chang
Summary: This study used tractography and diffusion kurtosis imaging (DKI) to evaluate cerebral white matter (WM) changes in patients with cerebrotendinous xanthomatosis (CTX) after stopping chenodeoxycholic acid (CDCA) treatment. The results showed that the changes in WM identified by tractography and DKI were correlated with the results of neuropsychiatric tests, suggesting their potential utility in assessing WM changes in CTX patients.
BIOMEDICAL JOURNAL
(2022)
Article
Genetics & Heredity
Gorka Fernandez-Eulate, Gilles C. Martin, Pascal Dureau, Claude Speeg-Spatz, Anais Brassier, Perrine Gillard, Dominique Bremond-Gignac, Dominique Thouvenin, Cecile Pagan, Foudil Lamari, Yann Nadjar
Summary: This study evaluated the utility of plasma cholestanol analysis at the moment of cataract diagnosis and before the onset of neurological impairment in patients with CTX. The study found that the incidence of CTX in the patient cohort was 3.3%, and moderate elevations of cholestanol levels may be associated with the occurrence of bilateral cataracts.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Philip Hoeflinger, Stefan Hauser, Eylan Yutuc, Holger Hengel, Lauren Griffiths, Florentine Radelfahr, Owain W. Howell, Yuqin Wang, Sonja L. Connor, P. Barton Duell, Andrea E. DeBarber, Peter Martus, Dieter Luetjohann, William J. Griffiths, Ludger Schols
Summary: Metabolic aberrations were identified in patients with CTX, with 7α,12α-dihydroxycholest-4-en-3-one and absence of 27-hydroxycholesterol suggested as potential sensitive metabolic biomarkers. Despite CDCA treatment reducing most accumulated metabolites, supplementation of 27-hydroxylated bile acid intermediates or replacement of CYP27A1 may be necessary to counter neurodegeneration in progressive CTX cases.
JOURNAL OF LIPID RESEARCH
(2021)
Article
Clinical Neurology
Min Young Chun, Nam Jin Heo, Sang Won Seo, Hyemin Jang, Yeon-Lim Suh, Ja-Hyun Jang, Young-Eun Kim, Eun-Joo Kim, So Young Moon, Na-Yeon Jung, Sun Min Lee, Hee Jin Kim
Summary: This report presents a case of Cerebrotendinous xanthomatosis (CTX) with an unusual phenotype of behavioral variant frontotemporal dementia (bvFTD) in middle age. Initial imaging showed high signal in the periventricular area and hypoperfusion in the frontal and temporal lobes. However, physical examination revealed xanthomas on the dorsum of the hands and Achilles tendons. Serum testing showed elevated cholesterol levels. Diagnosis of CTX was confirmed through detection of mutations in the CYP27A1 gene, and the patient was started on medication.
FRONTIERS IN NEUROLOGY
(2023)