Cerebrotendinous xanthomatosis: Clinical and biochemical evaluation of eight patients and review of the literature

Kuriyama, Masaru; Fujiyama, Jiro; Yoshidome, Hiroaki; Takenaga, Satoshi; Matsumuro, Kenji; Kasama, Takeshi; Fukuda, Katsutoshi; Kuramoto, Taiju; Hoshita, Takahiko; Seyama, Yousuke; Okatu, Yosuke; Osame, M

doi:10.1016/0022-510x(91)90073-g

Cited by 98 publications

(56 citation statements)

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“…Neurologic symptoms are an important clinical hallmark of CTX, are present in many cases at diagnosis, and distinguish CTX from other lipid disorders (e.g., familial hypercholesterolemia; sitosterolemia) (Moghadasian 2004). A broad range of neurologic findings have been reported in patients with CTX, with low intelligence, pyramidal signs (e.g., spasticity, hyperreflexia, extensor plantar responses), cerebellar signs (e.g., ataxia, dysarthria, (Berginer et al 1993); d (Berginer and Abeliovich 1981); e (Verrips et al 1999a); f (Waterreus et al 1987); g (Verrips et al 2000a); h (Berginer et al 1994) (Appadurai et al 2015) nystagmus), and peripheral neuropathy among the most common (Verrips et al 2000c;Pilo-de-la-Fuente et al 2011;Ly et al 2014); others include dementia, psychiatric symptoms, autism, epileptic seizures, and parkinsonism (e.g., spasticity, resting tremors) (Kuriyama et al 1991b;Verrips et al 2000c;Degos et al 2016;Berginer et al 2015;Stelten et al 2017). Symptoms reflecting neurologic dysfunction, such as intellectual disability and gait disturbances, are common presenting symptoms (Pilo-de-la-Fuente et al 2011).…”

Section: Clinical Presentationmentioning

confidence: 99%

Epidemiology, diagnosis, and treatment of cerebrotendinous xanthomatosis (CTX)

Salen

Steiner

2017

J of Inher Metab Disea

147

150

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Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disorder of bile acid synthesis caused by mutations in the cytochrome P450 CYP27A1 gene that result in production of a defective sterol 27‐hydroxylase enzyme. CTX is associated with abnormally high levels of cholestanol in the blood and accumulation of cholestanol and cholesterol in the brain, tendon xanthomas, and bile. Hallmark clinical manifestations of CTX include chronic diarrhea, bilateral cataracts, tendon xanthomas, and neurologic dysfunction. Although CTX is a rare disorder, it is thought to be underdiagnosed, as presenting signs and symptoms may be nonspecific with significant overlap with other more common conditions. There is marked variability in signs and symptoms, severity, and age of onset between patients. The disease course is progressive and potentially debilitating or fatal, particularly with respect to neurologic presentations that can include intellectual disability, autism, behavioral and psychiatric problems, and dementia, among others. Treatment with chenodeoxycholic acid (CDCA; chenodiol) is the current standard of care. CDCA can help restore normal sterol, bile acid, bile alcohol, and cholestanol levels. CDCA also appears to be generally effective in preventing adverse clinical manifestations of the disease from occurring or progressing if administered early enough. Improved screening and awareness of the condition may help facilitate early diagnosis and treatment.

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Section: Clinical Presentationmentioning

confidence: 99%

Epidemiology, diagnosis, and treatment of cerebrotendinous xanthomatosis (CTX)

Salen

Steiner

2017

J of Inher Metab Disea

147

150

View full text Add to dashboard Cite

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“…The availability of isotopically enriched CTX; for example, in an isolated Israeli Druze community, a carrier frequency of 1:11 for the deleterious c.355delC mutation was reported ( 7,8 ). Despite these observations, only around three hundred cases of CTX have been described worldwide ( 9 ), although large series of patients have been described by physicians with experience in recognizing the disorder in Italy ( 9,10 ), the Netherlands ( 3, 4 ), Japan ( 11 ), Spain ( 5 ), the United States, and Israel ( 12 ). CTX is likely not well recognized and under-or misdiagnosed.…”

mentioning

confidence: 99%

A blood test for cerebrotendinous xanthomatosis with potential for disease detection in newborns

DeBarber

Luo

Star-Weinstock³

et al. 2014

Journal of Lipid Research

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“…The importance of this oxidative mechanism for cholesterol homeostasis may be illustrated by the fact that subjects with a genetic disease lacking sterol 27-hydroxylase (cerebrotendinous xanthomatosis, CTX) 1 may get premature atherosclerosis despite normal circulating levels of cholesterol (4).…”

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confidence: 99%

Elimination of Cholesterol in Macrophages and Endothelial Cells by the Sterol 27-Hydroxylase Mechanism

Babiker

Andersson

Lund

et al. 1997

Journal of Biological Chemistry

222

165

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Cultured macrophages and endothelial cells have been reported to secrete 27-oxygenated metabolites of cholesterol. This mechanism was compared with the classical high density lipoprotein (HDL)-dependent reverse cholesterol transport. Under standard conditions, macrophage preparations had considerably higher capacity to secrete 27-hydroxycholesterol and 3␤-hydroxy-5-cholestenoic acid than had endothelial cells and fibroblasts. Western blotting showed that lung macrophages contained the most sterol 27-hydroxylase protein of the cells tested. The relative amounts of 3␤-hydroxy-5-cholestenoic acid produced by the macrophages were also highest. Macrophages derived from monocytes of patients with sterol 27-hydroxylase deficiency did not secrete 27-oxygenated products, demonstrating that sterol 27-hydroxylase is the critical enzyme for the conversion of cholesterol into the 27-oxygenated steroids. That sterol 27-hydroxylase is responsible not only for 27-hydroxylation of cholesterol but also for the further oxidation of this steroid into 3␤-hydroxy-5-cholestenoic acid was shown with use of tritium-labeled 27-hydroxycholesterol and an inhibitor of sterol 27-hydroxylase.Secretion of 27-oxygenated products by the cultured macrophages as well as the ratio between the alcohol and the acid appeared to be dependent upon total 27-hydroxylase activity, the availability of substrate cholesterol, and the presence of an acceptor for 27-hydroxycholesterol in the medium. With albumin as extracellular acceptor, the major secreted product was 3␤-hydroxy-5-cholestenoic acid. Under such conditions, secretion of labeled 27-oxygenated products was higher than that of labeled cholesterol from lung alveolar macrophages preloaded with [4-14 C]cholesterol. With HDL as acceptor, 27-hydroxycholesterol was the major secreted product, and the total secretion of labeled 27-oxygenated products was only about 10% of that of labeled cholesterol. Thus, 27-hydroxycholesterol and cholesterol may compete for HDL-mediated efflux from the cells.The results support the contention that the sterol 27-hydroxylase-mediated elimination of cholesterol is more important in macrophages than in endothelial cells. This mechanism may be an alternative and/or a complement to the classical HDL-mediated reverse cholesterol transport in macrophages, in particular when the concentration of HDL is low.

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Cerebrotendinous xanthomatosis: Clinical and biochemical evaluation of eight patients and review of the literature

Cited by 98 publications

References 50 publications

Epidemiology, diagnosis, and treatment of cerebrotendinous xanthomatosis (CTX)

Epidemiology, diagnosis, and treatment of cerebrotendinous xanthomatosis (CTX)

A blood test for cerebrotendinous xanthomatosis with potential for disease detection in newborns

Elimination of Cholesterol in Macrophages and Endothelial Cells by the Sterol 27-Hydroxylase Mechanism

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