Evoked Potentials in Cerebrotendinous Xanthomatosis and Effect Induced by Chenodeoxycholic Acid

Mondelli, Mauro; Rossi, Alessandro; Scarpini, Cinzia G.; Dotti, Maria Teresa; Federico, Antonio

doi:10.1001/archneur.1992.00530290051011

Cited by 45 publications

(19 citation statements)

References 17 publications

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“…It does, however, reduce abnormally elevated levels of cholestanol, apolipoprotein-B, apolipoprotein-A1, and albumin in the CSF and re-establishes the selective impermeability of the BBB . Improvements in neurophysiologic investigations: NCV and/or VEP (Ginanneschi et al 2013;Mondelli et al 1992;Mondelli et al 2001), EEG (Berginer et al 1984;van Heijst et al 1998), and bone mineral density (BMD) (Federico et al 1993;Martini et al 2013) have also been reported.…”

Section: Treatmentmentioning

confidence: 95%

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

Salen

Steiner

2017

J of Inher Metab Disea

139

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: 95%

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

Salen

Steiner

2017

J of Inher Metab Disea

139

150

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“…Cholestenoic acids regulate motor neuron survival via liver X receptors Spyridon Satish Srinivas Kitambi, 1 Andrew Lockhart, 3 Karin Tuschl, 4 Peter T. Clayton, 4 Andrew A. Morris, 5 Adelaida Martinez, 6 M. Ashwin Reddy, 7 Andrea Martinuzzi, 8 Maria T. Bassi, 9 Akira Honda, 10 Tatsuki Mizuochi, 11 Akihiko Kimura, 11 Hiroshi Nittono, 12 Giuseppe De Michele, 13 Rosa Carbone, 13 Chiara Criscuolo, 13 Joyce L. Yau, 14 Jonathan R. Seckl, 14 Rebecca Schüle, 15,16 Ludger Schöls, 15,16 Andreas W. Sailer, 17 Jens Kuhle, 18 Matthew J. Fraidakis, 19 Jan-Åke Gustafsson, 20,21 Knut R. Steffensen, 22 Ingemar Björkhem, 22 Patrik Ernfors, 1 Jan Sjövall, 1 Ernest Arenas, 1 and Yuqin Wang adult motor neurons, but also in their development (1). In agreement with these findings, enzymes involved in the synthesis of cholesterol and oxysterols, such as 2,3-oxidosqualene-lanosterol cyclase, are localized in islet-1 + oculomotor neurons in the mouse VM at E11.5 (1).…”

Section: Lxrbmentioning

confidence: 99%

“…In order to identify novel LXR ligands that regulate motor neuron function, we delved deeper into the human CSF sterolome and examined plasma of patients with 2 different human diseases associated with upper motor neuron degeneration, hereditary spastic paresis type 5 (SPG5) and cerebrotendinous xanthomatosis (CTX). These diseases result from mutations in the cytochrome P450 (CYP) genes CYP7B1 and CYP27A1, respectively (8)(9)(10)(11)(12)(13)(14)(15)(16)(17). The enzymes coded by these genes are responsible for 7α-hydroxylation of oxysterols and (25R),26-hydroxylation of sterols, respectively, reactions that generate further oxysterols and ultimately cholestenoic acids ( Figure 1A and ref.…”

Section: Lxrbmentioning

confidence: 99%

Cholestenoic acids regulate motor neuron survival via liver X receptors

Theofilopoulos¹,

Griffiths²,

Crick³

et al. 2014

J. Clin. Invest.

160

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tion-mass spectrometry (LC-ESI-MS) analysis. We hereby report the exact identity of 16 oxysterols and downstream metabolites, including cholestenoic acids, found in human CSF (Supplemental Table 1; supplemental material available online with this article; doi:10.1172/JCI68506DS1). The most abundant of these metabolites (19.48-0.40 ng/ml; Supplemental Figure 1) were 7α-hydroxy-3-oxocholest-4-en-26-oic acid (7αH,3O-CA), 3β-hydroxycholest-5-en-26-oic acid (3β-HCA), and 2 newly identified metabolites in CSF, 3β,7α-diHCA and 3β,7β-dihydroxycholest-5-en-26-oic acid (3β,7β-diHCA). Precursors of these acids, including 26-HC and newly identified 7α,26-dihydroxycholesterol (7α,26-diHC; cholest-5-ene-3β,7α,26-triol) and 7α,26-dihydroxycholest-4-en-3-one (7α,26-diHCO), were also found, but at lower levels (0.15-0.03 ng/ml). Our results thus identified 4 novel oxysterol metabolites in human CSF that were downstream of 26-HC ( Figure 1A). 26-HC is metabolized via 7α,26-diHC and 7α,26-diHCO, or via 3β-HCA and 3β,7α-diHCA, to 7αH,3O-CA. While 26-HC can cross the blood-brain barrier (BBB) and enter the brain from the circulation (25), 7αH,3O-CA traverses the BBB and is exported from the brain (26). Very low levels of 24S-hydroxycholesterol (24S-HC; cholest-5-ene-3β,24S-diol), 25-hydroxycholesterol (25-HC; cholest-5-ene-3β,25-diol), and newly identified 7α,25-dihydroxycholesterol (7α,25-diHC; cholest-5-ene-3β,7α,25-triol) and 7α,25-dihydroxycholest-4-en-3-one (7α,25-diHCO) were also found in CSF (0.08-0.03 ng/ml).Reduced levels of 7α-hydroxylated cholestenoic acids in CSF and plasma/serum of human patients with SPG5. SPG5 presents with upper motor neuron signs and results from mutations in CYP7B1, encoding the oxysterol 7α-hydroxylase responsible for 7α-hydroxylation of side-chain oxidized sterols that is required for extrahepatic synthesis of 7αH,3O-CA and its precursor, 3β,7α-diHCA ( Figure 1A and ref. 18). In order to examine the pathogenic role of such mutations, we sought to identify alterations in oxysterol and cholestenoic acid profiles in CSF and plasma from these patients and then examine the biological activities of the altered metabolites. We first studied the CSF from 3 patients with SPG5

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“…También suprime la biosíntesis de colestanol, normalizándose sus concentraciones en plasma y líquido cefalorraquídeo. Este tratamiento mejora las manifestaciones neurológi-cas 27,28 , manifestaciones sistémicas como los xantomas [29][30][31][32] e incluso la osteoporosis 33 . Desafortunadamente no hay disponibilidad del medicamento en Chile por lo que en este caso fue necesario importarlo.…”

Section: Discussionunclassified

Xantomatosis cerebrotendínea: Una causa de aumento de volumen bilateral del tendón de Aquiles. Caso clínico

Filippi

et al. 2009

Rev. méd. Chile

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Evoked Potentials in Cerebrotendinous Xanthomatosis and Effect Induced by Chenodeoxycholic Acid

Cited by 45 publications

References 17 publications

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

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

Cholestenoic acids regulate motor neuron survival via liver X receptors

Xantomatosis cerebrotendínea: Una causa de aumento de volumen bilateral del tendón de Aquiles. Caso clínico

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