Case Presentation

A Rare Symptomatic Case of Heterozygous Cerebro-Tendinous Xanthomatosis (CTX) Treated with Urso-Deoxycholic Acid (UDCA): With Mini Review

Madhuri Behari*

Published: 27 May, 2024 | Volume 8 - Issue 1 | Pages: 057-063

Cerebrotendinous Xanthamatosis (CTX) is a rare autosomal recessive disorder caused by a mutation in the CYP27A1 gene leading to impaired metabolism of cholesterol and accumulation of cholestenol and the cholesterol in various tissues such as the brain, eyes, lungs and bones and reduced formation of cheno-deoxycholic acid (CDCA). The clinical presentation is diverse, starting in the early neonatal period and progressing till adulthood unless treated early. A common neurological manifestation is a spino-cerebellar ataxia followed by spastic paraparesis. Tendon xanthoma is a classical finding that usually helps in clinching the diagnosis but may not be present in all cases. Brain MRI also reveals characteristic abnormalities with cerebellar atrophy and hyper-intensities in the dentate nucleus and surrounding cerebellar white matter on T1weighted images. It is a rare cause of treatable ataxia in young individuals. Treatment is by replacement by CDCA or Urso-deoxycholic acid (UDCA). Supplemented with statins these individuals also have premature atherosclerosis causing death due to athero-sclerotic coronary artery disease. Here a rare case of symptomatic heterologous CYP27A1 mutation is reported with syndrome of spino-cerebellar ataxia treated with UDCA.

Read Full Article HTML DOI: 10.29328/journal.jnnd.1001098 Cite this Article Read Full Article PDF


CYP27A1 mutation; Cholestenol; Cheno-deoxycholic acid; Urso-deoxycholic acid; Spino-cerebellar ataxia; Atherosclerosis; Cataract; Cholestatic jaundice


  1. Cali JJ, Hsieh CL, Francke U, Russell DW. Mutations in the bile acid biosynthetic enzyme sterol 27-hydroxylase underlie cerebrotendinous xanthomatosis. J Biol Chem. 1991 Apr 25;266(12):7779-83. PMID: 2019602; PMCID: PMC4449724.
  2. Federico A, Gallus GN. Cerebrotendinous Xanthomatosis. 2003 Jul 16 [Updated 2022 Mar 17]. In: Adam MP, Mirzaa GM, Pagon RA, et al. [] GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023.
Bookshelf URL: https://www.ncbi.nlm.nih.gov/books/
  3. Dutta AK, Danda S, Muthusamy K, Alexander M, Sudhakar SV, Hansdak S, Bandyopadhyay R, Bakhya Shree GB, Rekha L. Cerebrotendinous xanthomatosis: Possibility of founder mutation in CYP27A1 gene (c.526delG) in Eastern Indian and Surinamese population. Mol Genet Metab Rep. 2015 Mar 23;3:33-5. doi: 10.1016/j.ymgmr.2015.03.002. PMID: 26937392; PMCID: PMC4750635.
  4. Mirzanli C, Esenyel CZ, Ozturk K, Baris A, Imren Y. Cerebrotendinous xanthomatosis presenting with bilateral achilles tendon xanthomata: a case report. J Am Podiatr Med Assoc. 2013 Mar-Apr;103(2):152-5. doi: 10.7547/1030152. PMID: 23536508.
  5. Chowdhury G, Kayasthagir PK, Chowdhury A. Cerebrotendinous xanthomatosis: case report on a rare genetic case. JCMCTA. 2017;28(1):72-75.
  6. Shaji B, Srikumar B, Ramachandran D. A Preventable Ataxia: Cerebrotendinous Xanthomatosis. Ann Indian Acad Neurol. 2019 Oct-Dec;22(4):493-496. doi: 10.4103/aian.AIAN_126_18. Epub 2019 Oct 25. PMID: 31736580; PMCID: PMC6839296.
  7. Kimura S, Beppu T, Kugai N, Koide Y, Fujita T, Iida K, Yamashita N, Yamashita K, Seyama Y. A case of cerebrotendinous xanthomatosis: effects of ursodeoxycholic acid administration on serum bile acids and cholestanol. Jpn J Med. 1982 Jul;21(3):210-5. doi: 10.2169/internalmedicine1962.21.210. PMID: 7143816.
  8. Abe R, Sekijima Y, Kinoshita T, Yoshinaga T, Koyama S, Kato T, Ikeda SI. Spinal form cerebrotendinous xanthomatosis patient with long spinal cord lesion. J Spinal Cord Med. 2016 Nov;39(6):726-729. doi: 10.1179/1079026815Z.000000000409. Epub 2016 Feb 25. PMID: 25941960; PMCID: PMC5137569.
  9. Waterreus RJ, Koopman BJ, Wolthers BG, Oosterhuis HJ. Cerebrotendinous xanthomatosis (CTX): a clinical survey of the patient population in The Netherlands. Clin Neurol Neurosurg. 1987;89(3):169-75. doi: 10.1016/s0303-8467(87)80050-1. PMID: 3665290.
  10. Kuriyama M, Tokimura Y, Fujiyama J, Utatsu Y, Osame M. Treatment of cerebrotendinous xanthomatosis: effects of chenodeoxycholic acid, pravastatin, and combined use. J Neurol Sci. 1994 Aug;125(1):22-8. doi: 10.1016/0022-510x(94)90237-2. PMID: 7964884.
  11. Huidekoper HH, Vaz FM, Verrips A, Bosch AM. Hepatotoxicity due to chenodeoxycholic acid supplementation in an infant with cerebrotendinous xanthomatosis: implications for treatment. Eur J Pediatr. 2016 Jan;175(1):143-6. doi: 10.1007/s00431-015-2584-7. Epub 2015 Jul 10. PMID: 26156051; PMCID: PMC4709371.
  12. Lee SH, Jang DK, Yoo MW, Hwang SH, Ryu SY, Kwon OK, Hur H, Man Yoon H, Eom BW, Ahn HS, Son T, Song KY, Lee HH, Choi MG, An JY, Lee SI, Lee KH, Ahn S, Park YS, Park DJ; Efficacy and Safety of DWJ1319 in the Prevention of Gallstone Formation after Gastrectomy in Patient with Gastric Cancer: A Multicenter, Randomized, Double-blind, Placebo-controlled Study (PEGASUS-D) Group. Efficacy and Safety of Ursodeoxycholic Acid for the Prevention of Gallstone Formation After Gastrectomy in Patients With Gastric Cancer: The PEGASUS-D Randomized Clinical Trial. JAMA Surg. 2020 Aug 1;155(8):703-711. doi: 10.1001/jamasurg.2020.1501. PMID: 32584935; PMCID: PMC7301302.
  13. Stelten BML, Dotti MT, Verrips A, Elibol B, Falik-Zaccai TC, Hanman K, Mignarri A, Sithole B, Steiner RD, Verma S, Yahalom G, Zubarioglu T, Mochel F, Federico A. Expert opinion on diagnosing, treating and managing patients with cerebrotendinous xanthomatosis (CTX): a modified Delphi study.Orphanet J Rare Dis. 2021; 16:353.
  14. Menkes JH, Schimschock JR, Swanson PD. Cerebrotendinous xanthomatosis. The storage of cholestanol within the nervous system. Arch Neurol. 1968 Jul;19(1):47-53. doi: 10.1001/archneur.1968.00480010065004. PMID: 5676919.
  15. Salen G, Steiner RD. Epidemiology, diagnosis, and treatment of Cerebrotendinous Xanthomatosis (CTX). J Inherit Metab Dis. 2017; 40: 771–81. doi: 10.1007/s10545-017-0093-8
  16. Appadurai V, DeBarber A, Chiang PW, Patel SB, Steiner RD, Tyler C, Bonnen PE. Apparent underdiagnosis of Cerebrotendinous Xanthomatosis revealed by analysis of ~60,000 human exomes. Mol Genet Metab. 2015 Dec;116(4):298-304. doi: 10.1016/j.ymgme.2015.10.010. Epub 2015 Oct 26. PMID: 26643207; PMCID: PMC4767010.
  17. Verrips A, Hoefsloot LH, Steenbergen GC, Theelen JP, Wevers RA, Gabreëls FJ, van Engelen BG, van den Heuvel LP. Clinical and molecular genetic characteristics of patients with cerebrotendinous xanthomatosis. Brain. 2000 May;123 ( Pt 5):908-19. doi: 10.1093/brain/123.5.908. PMID: 10775536.
  18. Edwards PA, Kast HR, Anisfeld AM. BAREing it all: the adoption of LXR and FXR and their roles in lipid homeostasis. J Lipid Res. 2002 Jan;43(1):2-12. PMID: 11792716.
  19. von Bahr S, Björkhem I, Van't Hooft F, Alvelius G, Nemeth A, Sjövall J, Fischler B. Mutation in the sterol 27-hydroxylase gene associated with fatal cholestasis in infancy. J Pediatr Gastroenterol Nutr. 2005 Apr;40(4):481-6. doi: 10.1097/01.mpg.0000150419.23031.2a. Erratum in: J Pediatr Gastroenterol Nutr. 2005 Jul;41(1):144. PMID: 15795599.
  20. Cruysberg JR, Wevers RA, van Engelen BG, Pinckers A, van Spreeken A, Tolboom JJ. Ocular and systemic manifestations of cerebrotendinous xanthomatosis. Am J Ophthalmol. 1995 Nov;120(5):597-604. doi: 10.1016/s0002-9394(14)72206-8. PMID: 7485361.
  21. Mignarri A, Gallus GN, Dotti MT, Federico A. A suspicion index for early diagnosis and treatment of cerebrotendinous xanthomatosis. J Inherit Metab Dis. 2014 May;37(3):421-9. doi: 10.1007/s10545-013-9674-3. Epub 2014 Jan 18. PMID: 24442603.
  22. Sekijima Y, Koyama S, Yoshinaga T, Koinuma M, Inaba Y. Nationwide survey on cerebrotendinous xanthomatosis in Japan. J Hum Genet. 2018 Mar;63(3):271-280. doi: 10.1038/s10038-017-0389-4. Epub 2018 Jan 10. PMID: 29321515.
  23. Brienza M, Fiermonte G, Cambieri C, Mignarri A, Dotti MT, Fiorelli M. Enlarging brain xanthomas in a patient with cerebrotendinous xanthomatosis. J Inherit Metab Dis. 2015 Sep;38(5):981-2. doi: 10.1007/s10545-014-9805-5. Epub 2015 Jan 8. PMID: 25567502.
  24. Nie S, Chen G, Cao X, Zhang Y. Cerebrotendinous Xanthomatosis: a comprehensive review of pathogenesis, clinical manifestations, diagnosis, and management. Orphanet J Rare Dis. 2014; 9: 179. doi: 10.1186/s13023-014-0179-4.
  25. Wong JC, Walsh K, Hayden D, Eichler FS. Natural history of neurological abnormalities in cerebrotendinous xanthomatosis. J Inherit Metab Dis. 2018 Jul;41(4):647-656. doi: 10.1007/s10545-018-0152-9. Epub 2018 Feb 26. PMID: 29484516.
  26. Bartholdi D, Zumsteg D, Verrips A, Wevers RA, Sistermans E, Hess K, Jung HH. Spinal phenotype of cerebrotendinous xanthomatosis--a pitfall in the diagnosis of multiple sclerosis. J Neurol. 2004 Jan;251(1):105-7. doi: 10.1007/s00415-004-0221-x. PMID: 14999499.
  27. Mutlu D, Tuncer A, Gocmen R, Yalcin-Cakmakli G, Saygı S, Elibol B: Diagnostic challenge: A case of late- Bartholdi D, Zumsteg D, Verrips A, Wevers RA, Sistermans E, Hess K, Jung HH: Spinal phenotype of cerebrotendinous xanthomatosis--a pitfall in the diagnosis of multiple sclerosis. J Neurol, 2004; 251: 105-107
  28. Dotti MT, Lütjohann D, von Bergmann K, Federico A. Normalisation of serum cholestanol concentration in a patient with cerebrotendinous xanthomatosis by combined treatment with chenodeoxycholic acid, simvastatin and LDL apheresis. Neurol Sci. 2004 Oct;25(4):185-91. doi: 10.1007/s10072-004-0320-6. PMID: 15549503.
  29. Koopman BJ, Wolthers BG, van der Molen JC, Waterreus RJ. Bile acid therapies applied to patients suffering from cerebrotendinous xanthomatosis. Clin Chim Acta. 1985 Oct 31;152(1-2):115-22. doi: 10.1016/0009-8981(85)90182-2. PMID: 4053393.
  30. Zubarioglu T, Kiykim E, Yesil G, Demircioglu D, Cansever MS, Yalcinkaya C, Aktuglu-Zeybek C. Early diagnosed cerebrotendinous xanthomatosis patients: clinical, neuroradiological characteristics and therapy results of a single center from Turkey. Acta Neurol Belg. 2019 Sep;119(3):343-350. doi: 10.1007/s13760-017-0851-2. Epub 2017 Oct 22. PMID: 29058268.
  31. Lumbreras S, Ricobaraza A, Baila-Rueda L, Gonzalez-Aparicio M, Mora-Jimenez L, Uriarte I, Bunuales M, Avila MA, Monte MJ, Marin JJG, Cenarro A, Gonzalez-Aseguinolaza G, Hernandez-Alcoceba R. Gene supplementation of CYP27A1in the liver restores bile acid metabolism in a mouse model of cerebrotendinous xanthomatosis. Mol Ther Methods Clin Dev. 2021 Jul 21;22:210-221. doi: 10.1016/j.omtm.2021.07.002. PMID: 34485606; PMCID: PMC8399082.
  32. Verrips A, van Engelen BG, ter Laak H, Gabreëls-Festen A, Janssen A, Zwarts M, Wevers RA, Gabreëls FJ. Cerebrotendinous xanthomatosis. Controversies about nerve and muscle: observations in ten patients. Neuromuscul Disord. 2000 Aug;10(6):407-14. doi: 10.1016/s0960-8966(00)00112-7. PMID: 10899446.

  33. Federico A, Dotti MT, Volpi N. Muscle mitochondrial changes in cerebrotendinous xanthomatosis. Ann Neurol. 1991 Nov;30(5):734-5. doi: 10.1002/ana.410300517. PMID: 1763899.
  34. Kuriyama M, Fujiyama J, Yoshidome H, Takenaga S, Matsumuro K, Kasama T, Fukuda K, Kuramoto T, Hoshita T, Seyama Y, et al. Cerebrotendinous xanthomatosis: clinical and biochemical evaluation of eight patients and review of the literature. J Neurol Sci. 1991 Apr;102(2):225-32. doi: 10.1016/0022-510x(91)90073-g. PMID: 2072121.
  35. Valdivielso P, Calandra S, Durán JC, Garuti R, Herrera E, González P. Coronary heart disease in a patient with cerebrotendinous xanthomatosis. J Intern Med. 2004 Jun;255(6):680-3. doi: 10.1111/j.1365-2796.2004.01316.x. PMID: 15147532.
  36. Souto MJS, Almeida-Santos MA, Ferreira EJP, Gonçalves LFG, Oliveira JLM, Sousa ACS. Spontaneous Coronary Artery Dissection in a Patient with Cerebrotendinous Xanthomatosis. Arq Bras Cardiol. 2020 Apr;115(1 suppl 1):18-21. English, Portuguese. doi: 10.36660/abc.20190456. PMID: 32935759; PMCID: PMC8386949. 

  37. Potkin BN, Hoeg JM, Connor WE, Salen G, Quyyumi AA, Brush JE Jr, Roberts WC, Brewer HB Jr: Aneurysmal coronary artery disease in cerebrotendinous xanthomatosis. Am J Cardiol, 1988; 61: 1150-1152.
  38. Dotti MT, Mondillo S, Plewnia K, Agricola E, Federico A. Cerebrotendinous xanthomatosis: evidence of lipomatous hypertrophy of the atrial septum. J Neurol. 1998 Nov;245(11):723-6. doi: 10.1007/s004150050274. PMID: 9808240.
  39. Saute JA, Giugliani R, Merkens LS, Chiang JPW, DeBarber AE, de Souza CFM. Look carefully to the heels! a potentially treatable cause of spastic paraplegia. J Inherit Metab Dis. 2015; 38: 363–4. doi: 10.1007/s10545-014-9745-0
  40. Burguez D, Polese-Bonatto M, Scudeiro LAJ, Björkhem I, Schöls L, Jardim LB, Matte U, Saraiva-Pereira ML, Siebert M, Saute JAM. Clinical and molecular characterization of hereditary spastic paraplegias: A next-generation sequencing panel approach. J Neurol Sci. 2017 Dec 15;383:18-25. doi: 10.1016/j.jns.2017.10.010. Epub 2017 Oct 10. PMID: 29246610.
  41. Atallah I, Millán DS, Benoît W, Campos-Xavier B, Superti-Furga A, Tran C. Spinal cerebrotendinous xanthomatosis: A case report and literature review. Mol Genet Metab Rep. 2021 Feb 3;26:100719. doi: 10.1016/j.ymgmr.2021.100719. PMID: 33659184; PMCID: PMC7890005.
  42. Duell PB, Salen G, Eichler FS, DeBarber AE, Connor SL, Casaday L, Jayadev S, Kisanuki Y, Lekprasert P, Malloy MJ, Ramdhani RA, Ziajka PE, Quinn JF, Su KG, Geller AS, Diffenderfer MR, Schaefer EJ: Diagnosis, treatment, and clinical outcomes in 43 cases with cerebrotendinous xanthomatosis. J Clin Lipidol, 
2018; 12: 1169-1178.
  43. Jain RS, Sannegowda RB, Agrawal A, Hemrajani D, Jain R, Mathur T. ‘Hot cross bun’ sign in a case of cerebrotendinous xanthomatosis: a rare neuroimaging observation. BMJ Case Rep. 2013; doi: 10.1136/bcr- 2012-006641
  44. Berginer VM, Salen G, Shefer S. Long-term treatment of cerebrotendinous xanthomatosis with chenodeoxycholic acid. N Engl J Med. 1984 Dec 27;311(26):1649-52. doi: 10.1056/NEJM198412273112601. PMID: 6504105.
  45. van Heijst AF, Verrips A, Wevers RA, Cruysberg JR, Renier WO, Tolboom JJ. Treatment and follow-up of children with cerebrotendinous xanthomatosis. Eur J Pediatr. 1998 Apr;157(4):313-6. doi: 10.1007/s004310050818. PMID: 9578968.
  46. Pilo-de-la-Fuente B, Jimenez-Escrig A, Lorenzo JR, Pardo J, Arias M, Ares-Luque A, Duarte J, Muñiz-Pérez S, Sobrido MJ. Cerebrotendinous xanthomatosis in Spain: clinical, prognostic, and genetic survey. Eur J Neurol. 2011 Oct;18(10):1203-11. doi: 10.1111/j.1468-1331.2011.03439.x. Epub 2011 Jun 4. PMID: 21645175.
  47. Yahalom G, Tsabari R, Molshatzki N, Ephraty L, Cohen H, Hassin-Baer S. Neurological outcome in cerebrotendinous xanthomatosis treated with chenodeoxycholic acid: early versus late diagnosis. Clin Neuropharmacol. 2013 May-Jun;36(3):78-83. doi: 10.1097/WNF.0b013e318288076a. PMID: 23673909.
  48. Stelten BML, Huidekoper HH, van de Warrenburg BPC, Brilstra EH, Hollak CEM, Haak HR, Kluijtmans LAJ, Wevers RA, Verrips A. Long-term treatment effect in cerebrotendinous xanthomatosis depends on age at treatment start. Neurology. 2019 Jan 8;92(2):e83-e95. doi: 10.1212/WNL.0000000000006731. Epub 2018 Dec 7. PMID: 30530799.
  49. Ellis E, Axelson M, Abrahamsson A, Eggertsen G, Thörne A, Nowak G, Ericzon BG, Björkhem I, Einarsson C. Feedback regulation of bile acid synthesis in primary human hepatocytes: evidence that CDCA is the strongest inhibitor. Hepatology. 2003 Oct;38(4):930-8. doi: 10.1053/jhep.2003.50394. PMID: 14512880.
  50. Mandia D, Chaussenot A, Besson G, Lamari F, Castelnovo G, Curot J, Duval F, Giral P, Lecerf JM, Roland D, Pierdet H, Douillard C, Nadjar Y. Cholic acid as a treatment for cerebrotendinous xanthomatosis in adults. J Neurol. 2019 Aug;266(8):2043-2050. doi: 10.1007/s00415-019-09377-y. Epub 2019 May 21. PMID: 31115677.
  51. Pierre G, Setchell K, Blyth J, Preece MA, Chakrapani A, McKiernan P. Prospective treatment of cerebrotendinous xanthomatosis with cholic acid therapy. J Inherit Metab Dis. 2008 Dec;31 Suppl 2:S241-5. doi: 10.1007/s10545-008-0815-z. Epub 2008 Dec 27. PMID: 19125350.
  52. Kimura S, Beppu T, Kugai N, Koide Y, Fujita T, Iida K, Yamashita N, Yamashita K, Seyama Y. A case of cerebrotendinous xanthomatosis: effects of ursodeoxycholic acid administration on serum bile acids and cholestanol. Jpn J Med. 1982 Jul;21(3):210-5. doi: 10.2169/internalmedicine1962.21.210. PMID: 7143816.
  53. Verrips A, Wevers RA, Van Engelen BG, Keyser A, Wolthers BG, Barkhof F, Stalenhoef A, De Graaf R, Janssen-Zijlstra F, Van Spreeken A, Gabreëls FJ. Effect of simvastatin in addition to chenodeoxycholic acid in patients with cerebrotendinous xanthomatosis. Metabolism. 1999 Feb;48(2):233-8. doi: 10.1016/s0026-0495(99)90040-9. PMID: 10024088.
  54. Salen G, Batta AK, Tint GS, Shefer S. Comparative effects of lovastatin and chenodeoxycholic acid on plasma cholestanol levels and abnormal bile acid metabolism in cerebrotendinous xanthomatosis. Metabolism. 1994 Aug;43(8):1018-22. doi: 10.1016/0026-0495(94)90183-x. PMID: 8052141.


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