Treatment of cerebrotendinous xanthomatosis: effects of chenodeoxycholic acid, pravastatin, and combined use

Kuriyama, Masaru; Tokimura, Yoshika; Fujiyama, Jiro; Utatsu, Yasuhiko; Osame, Mitsuhiro

doi:10.1016/0022-510x(94)90237-2

Cited by 81 publications

(54 citation statements)

References 38 publications

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“…However, advanced symptoms that have been present for many years are unlikely to significantly improve (Berginer et al 2009). It reduces levels of circulating cholestanol, other sterols (e.g., lanosterol, campesterol, sitosterol), and bile acid precursors (e.g., 7-α-hydroxy-4-cholesten-3-one) (Berginer et al 1984;Kuriyama et al 1994;Salen et al 1975;Björkhem et al 1987;Mignarri et al 2016;DeBarber et al 2010); bile alcohol levels in plasma, bile, and urine (Batta et al 1987;Batta et al 2004); and cholic acid levels (Salen et al 1994). It increases CDCA levels in bile (Salen et al 1994), and normalizes lipid levels (Kuriyama et al 1994;Tint et al 1989).…”

Section: Treatmentmentioning

confidence: 99%

“…It reduces levels of circulating cholestanol, other sterols (e.g., lanosterol, campesterol, sitosterol), and bile acid precursors (e.g., 7-α-hydroxy-4-cholesten-3-one) (Berginer et al 1984;Kuriyama et al 1994;Salen et al 1975;Björkhem et al 1987;Mignarri et al 2016;DeBarber et al 2010); bile alcohol levels in plasma, bile, and urine (Batta et al 1987;Batta et al 2004); and cholic acid levels (Salen et al 1994). It increases CDCA levels in bile (Salen et al 1994), and normalizes lipid levels (Kuriyama et al 1994;Tint et al 1989). CDCA treatment typically does not significantly reduce tendon xanthomas or improve cataracts (Berginer et al 1984;Mondelli et al 2001), but can stabilize or improve neurologic manifestations, including cognitive deterioration, pyramidal tract signs, and cerebellar deficits (Berginer et al 1984;Mondelli et al 2001;van Heijst et al 1998).…”

Section: Treatmentmentioning

confidence: 99%

“…Hepatotoxicity has been specifically but rarely reported. One patient in a small study of combined CDCA and pravastatin treatment had to discontinue CDCA due to liver dysfunction after 6 months (Kuriyama et al 1994). Another study reported that one patient switched from CDCA to cholic acid treatment due to side effects of severe diarrhea, nausea, and abnormal liver tests (Waterreus et al 1987).…”

Section: Treatmentmentioning

confidence: 99%

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

Salen

Steiner

2017

J of Inher Metab Disea

130

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: Treatmentmentioning

confidence: 99%

Section: Treatmentmentioning

confidence: 99%

Section: Treatmentmentioning

confidence: 99%

See 1 more Smart Citation

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

Salen

Steiner

2017

J of Inher Metab Disea

130

150

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“…In addition, BA administration (e.g., chenodeoxycholic acid, CDCA) to patients with gallstones or cerebrotendinous xanthomatosis (CTX) decreases HDL-C ( 13,14 ). These metabolic effects have thus far been attributed to the suppression of apoA-I expression by BA-mediated FXR activation ( 11 ), while a potential contribution of CETP to the shift in plasma lipoprotein profi les in patients with elevated plasma BA has not been explored.…”

Section: Measurement Of Cetp Activitymentioning

confidence: 99%

Farnesoid X receptor activation increases cholesteryl ester transfer protein expression in humans and transgenic mice

Gautier

Haan

Grober

et al. 2013

Journal of Lipid Research

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The cholesteryl ester transfer protein (CETP) promotes the heteroexchange of cholesteryl esters and triglycerides (TG) between plasma high density lipoproteins (HDL) and apoB-containing lipoproteins, resulting in a proatherogenic plasma lipid profi le with increased VLDL and LDL cholesterol levels and decreased HDL cholesterol (HDL-C) ( 1, 2 ). Given the key importance of dyslipidemia for the development of atherosclerosis ( 3 ), most ( 1, 2, 4-6 ) but Abstract Cholesteryl ester transfer protein (CETP) activity results in a proatherogenic lipoprotein profi le. In cholestatic conditions, farnesoid X receptor (FXR) signaling by bile acids (BA) is activated and plasma HDL cholesterol (HDL-C) levels are low. This study tested the hypothesis that FXR-mediated induction of CETP contributes to this phenotype. Patients with cholestasis and high plasma BA had lower HDL-C levels and higher plasma CETP activity and mass compared with matched controls with low plasma BA (each P < 0.01). BA feeding in APOE3*Leiden transgenic mice expressing the human CETP transgene controlled by its endogenous promoter increased cholesterol within apoBcontaining lipoproteins and decreased HDL-C (each P < 0.01), while hepatic CETP mRNA expression and plasma CETP activity and mass increased (each P < 0.01). In vitro studies confi rmed that FXR agonists substantially augmented CETP mRNA expression in hepatocytes and macrophages dependent on functional FXR expression (each P < 0.001). These transcriptional effects are likely mediated by an ER8 FXR response element (FXRE) in the fi rst intron. In conclusion, using a translational approach, this study identifi es CETP as novel FXR target gene. By increasing CETP expression, FXR activation leads to a proatherogenic

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“…28 The combination of CDCA and pravastatin was a good treatment for CTX, based on the improvement of serum lipoprotein metabolism, the suppression of cholesterol synthesis, and reductions of cholestanol and plant sterol levels. In all patients, the progression of disease was arrested, but dramatic effects on clinical manifestations, xanthoma, and electrophysiological findings could not be found after the treatment of these drugs.…”

Section: Imds Involving the Lensmentioning

confidence: 99%

Inherited metabolic disorders involving the eye: a clinico-biochemical perspective

Rajappa

Goyal

Kaur

2009

Eye

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The diagnosis of inborn errors of metabolism is challenging for most physicians. Improvements in medical technology and greater knowledge of the human genome are resulting in significant changes in the diagnosis, classification, and treatment of inherited metabolic disorders (IMDs). Many known inborn errors of metabolism will be recognised earlier or treated differently because of these changes. It is important that physicians recognise the clinical signs of IMDs and know when to propose advanced laboratory testing or referral to a higher centre for better patient management. Ocular manifestations occur in various metabolic disorders. Although there is an extensive understanding of many inborn errors of metabolism at the biochemical, molecular, and metabolic levels, little is known about their pathogenesis. In particular, how systemic metabolic disease contributes to ocular defects remains to be elucidated in IMDs. The occurrence of eye abnormalities could be due to direct toxic mechanisms of abnormal metabolic products or accumulation of normal metabolites by errors of synthetic pathways or by deficient energy metabolism. A detailed ophthalmological assessment is essential. Definitive diagnosis and management of patients with IMDs is ideally carried out by a combination of specialists, including an ophthalmologist, paediatrician, biochemist, and medical geneticist. Recent advances in the diagnosis and treatment of IMDs have substantially improved the prognosis for many of these conditions.

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Treatment of cerebrotendinous xanthomatosis: effects of chenodeoxycholic acid, pravastatin, and combined use

Cited by 81 publications

References 38 publications

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

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

Farnesoid X receptor activation increases cholesteryl ester transfer protein expression in humans and transgenic mice

Inherited metabolic disorders involving the eye: a clinico-biochemical perspective

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