Cerebrotendinous xanthomatosis (CTX), also called cerebral cholesterosis,[1] is a rare inborn bile acid metabolism disorder caused by autosomal-recessive mutations in the CYP27A1 gene.[2] CTX is characterized by a wide range of symptoms, including neurological and non-neurological issues.
CTX management includes surgery, replacement therapy, and additional symptomatic treatment. Bile acids like taurocholic acid, ursodeoxycholic acid (UDCA), cholic acid, and chenodeoxycholic acid (CDCA) are often used. CDCA treatment is preferred for both neurological and non-neurological symptoms. Symptomatic treatment is crucial due to the wide range of symptoms associated with CTX.
Cerebrotendinous xanthomatosis manifests in a variety of ways, including several organs and a wide spectrum of neurological and non-neurological symptoms.[3] For CTX patients, the average age of symptom onset is 19 years.[4]
One common indicator of CTX is cataract that develops in childhood.[7] It has been highlighted that this is an early symptom that comes before neurological symptoms and tendon xanthoma, and it is thought to be helpful for an early diagnosis.[2] Adults with CTX frequently have cataracts and optic disk paleness as well.[8] Other ocular problems associated with CTX include deposits that resemble cholesterol and retinal vessel sclerosis.[9]
Patients with CTX frequently have osteoporosis and recurrent bone fractures as clinical symptoms. Patients with significant gait abnormalities who have little bone mass are more likely to fall and break their bones accidentally.[2] In CTX patients, serum calcium, phosphate, and vitamin D metabolites are normal, but intestine radiocalcium absorption is reduced and total body bone mineral density is poor.[13]
In individuals with cerebrotendinous xanthomatosis, xanthomas frequently develop in the second or third decade of life, while they can occasionally not develop at all. They usually originate on the Achilles tendons, although they have also been discovered in the lungs, bones, and central nervous system, as well as on the extensor tendons of the elbow, hand, patellar tendon, and neck.[8]
Molecular genetic analysis, neuroimaging, biochemical testing, and clinical findings are the main methods used in the diagnosis of CTX. When individuals present with neurological symptoms beginning in childhood with xanthomas, a CTX diagnosis should be taken into consideration.[2]
Enhanced plasma cholestanol and elevated bile alcohol levels in urine, along with a decreased biliary concentration of chenodeoxycholic acid, are among the biochemical anomalies observed in CTX patients.[19] Another characteristic of CTX is an increased plasma level of cholestanol.[20]
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^Dotti, Maria Teresa; Mondillo, Sergio; Plewnia, Katrin; Agricola, Eustachio; Federico, A. (1998-10-01). "Cerebrotendinous xanthomatosis: evidence of lipomatous hypertrophy of the atrial septum". Journal of Neurology. 245 (11). Springer Science and Business Media LLC: 723–726. doi:10.1007/s004150050274. ISSN0340-5354. PMID9808240.
^Weingärtner, Oliver; Laufs, Ulrich; Böhm, Michael; Lütjohann, Dieter (2010). "An alternative pathway of reverse cholesterol transport: The oxysterol 27-hydroxycholesterol". Atherosclerosis. 209 (1). Elsevier BV: 39–41. doi:10.1016/j.atherosclerosis.2009.09.015. ISSN0021-9150. PMID19801147.
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^Mignarri, Andrea; Gallus, Gian Nicola; Dotti, Maria Teresa; Federico, Antonio (2014-01-18). "A suspicion index for early diagnosis and treatment of cerebrotendinous xanthomatosis". Journal of Inherited Metabolic Disease. 37 (3). Wiley: 421–429. doi:10.1007/s10545-013-9674-3. ISSN0141-8955. PMID24442603.
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