Serebrotendinöz Ksantomatozis
Özet
Serebrotendinöz ksantomatozis; CYP27A1 genindeki mutasyonlar sonucu gelişen, safra asidi sentez bozukluğuyla karakterize nadir ve otozomal resesif bir lipid depo hastalığıdır. Hastalık; santral sinir sistemi, tendonlar ve diğer dokularda kolesterol ve kolestanol birikimiyle seyrederek katarakt, kronik ishal, erken ateroskleroz ve ciddi nörolojik bozukluklara yol açar. Erken dönemde teşhis edilmesi ve kenodeoksikolik asit tedavisine başlanması, klinik tablonun kötüleşmesini önlemek ve semptomları iyileştirmek için hayati önem taşır. Hastalık ilerleyici doğası nedeniyle erken tanı, genetik danışmanlık ve uygun tedavi yöntemleriyle kontrol altına alınmalıdır.
Cerebrotendinous xanthomatosis is a rare, autosomal recessive lipid storage disease characterized by a bile acid synthesis disorder resulting from mutations in the CYP27A1 gene. The condition leads to the accumulation of cholesterol and cholestanol in the central nervous system, tendons, and other tissues, manifesting as cataracts, chronic diarrhea, premature atherosclerosis, and severe neurological deficits. Early diagnosis and prompt treatment with chenodeoxycholic acid are critical to preventing progressive multi-organ damage and managing the neurological symptoms. Given its progressive nature, effective management relies on early detection, genetic counseling, and timely therapeutic intervention.
Referanslar
Clayton PT. Disorders of Bile Acid Synthesis. In: Saudubray JM, Baumgartner MR, Walter J, eds. Inborn Metabolic Diseases. Diagnosis and Treatment, 6th ed. Berlin Heidelberg: Springer-Verlag; 2016: 469–71.
Salen G, Steiner RD. Epidemiology, diagnosis, and treatment of cerebrotendinous xanthomatosis (CTX). J Inherit Metab Dis. 2017;40(6):771-781.
Patni N, Wilson DP, Feingold KR et al. Cerebrotendinous Xanthomatosis. In: Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-2020.PMID:27809439.
Waldman AT. Cerebrotendinous xanthomatosis. In: Gonzales-Scarano F, Patterson MC eds. Up to date. Literature review current through: Feb 2021. www.uptodate.com. 2021
Van Bogaert L, Scherer H, Epstein E. Une Forme Cerebrale de la Cholesterinose Generalisee. Paris: Masson et Cie;1937
Cali JJ, Hsieh C-L, Francke U, Russell DW. Mutations in the bile acid biosynthetic enzyme sterol 27-hydroxylase underlie cerebrotendinous xanthomatosis. J Biol Chem. 1991; 266:7779–7783
Lipiński P, Klaudel-Dreszler M, Ciara E et al. Sterol 27-Hydroxylase Deficiency as a Cause of Neonatal Cholestasis: Report of 2 Cases and Review of the Literature. Front Pediatr. 2021;13;8:616582.
Nie S, Chen G, Xubeing Cao X, Zhang Y. Cerebrotendinous xanthomatosis: a comprehensive review of pathogenesis, clinical manifestations, diagnosis, and management. Orphanet journal of rare diseases. 2014; 26;9:179.
Lorincz MT, Rainier S, Thomas D, Fink JK. Cerebrotendinous xanthomatosis – Possible higher prevalence than previously recognized. Arch Neurol. 2005; 62: 1459-1463.
Appadurai V, De Barber A, Chiang PW et al. Apparent underdiagnosis of Cerebrotendinous Xanthomatosis revealed by analysis of ~60,000 human exomes. Mol Genet Metab. 2015;116(4):298-304.
Pilo-de-la-Fuente B, Jimenez-Escrig A, Lorenzo JR et al. Cerebrotendinous xanthomatosis in Spain: clinical, prognostic, and genetic survey. European Journal of Neurology 2011, 18: 1203–1211.
Berginer VM and Abeliovich D. Genetics of Cerebrotendinous Xanthomatosis (CTX): An Autosomal Recessive Trait With High Gene Frequency in Sephardim of Moroccan Origin.American Journal of Medical Genetics.1981; 10:151-157.
Falik-Zaccai TC, Kfir N, Frenkel P et al. Population screening in a Druze community: the challenge and the reward. Genet Med. 2008;10(12):903-9.
Rosner G, Rosner S and Orr-Urtreger A. Genetic Testing in Israel: An Overview. Annu Rev Genomics Hum Genet. 2009;10:175-92.
Cali JJ, Russell DW. Characterisation of human sterol 27-hydroxylase: a mitochondrial cytochrome P-450 that catalyses multiple oxidations in bile acid biosynthesis. J Biol Chem 1991; 266:7774–7778
Clayton PT, Casteels M, Mieli-Vergani G, Lawson AM. Familial giant cell hepatitis with low bile acid concentrations and increased urinary excretion of specific bile alcohols: a new inborn error of bile acid synthesis? Pediatr Res. 1995;37:424–431
Panzenboeck U, Andersson U, Hansson M, Sattler W, Meaney S, Björkhem I. On the mechanism of cerebral accumulation of cholestanol in patients with cerebrotendinous xanthomatosis. J Lipid. Res 2007;48:1167–1174
Degrassi I, Amoruso C, Giordano G et al. Case Report: Early Treatment With Chenodeoxycholic Acid in Cerebrotendinous Xanthomatosis Presenting as Neonatal Cholestasis. Front Pediatr.2020;16;8:382.
Federico A, Dotti MT, Gallus GN. Cerebrotendinous Xanthomatosis. 2003 Jul 16 [Updated 2016 Apr 14]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021.
Federico A, Dotti MT, Loré F, Nuti R. Cerebrotendinous xanthomatosis: pathophysiological study on bone metabolism. J Neurol Sci 1993; 115:67.
Saussy K, Jain N, Murina A. Cerebrotendinous xanthomatosis: A report of 3 cases. JAAD Case Rep. 2020;16;6(12):1205-1207.
Yunisova G, Tufekcioglu Z, Dogu O et al. Patients with Lately Diagnosed Cerebrotendinous Xanthomatosis. Neurodegener Dis.2019;19(5-6):218-224.
Mukaino A, Tsuda M, Yamashita S, Kosaka T, Wada K, Ando Y. Cerebrotendinous xanthomatosis presenting with extensive cerebral cortex symptoms: A case report. Clin Neurol Neurosurg. 2018;174:217-219.
Kamaşak T, Demirhan YN, Parıltan Kücükalioglu B et al. A Rare Metabolic Disease: Cerebrotendinous Xanthomatosis. Van Medical journal 2019; 26(2): 265-267.
Zhang S, Li W, Zheng R et al. Cerebrotendinous xanthomatosis with peripheral neuropathy: a clinical and neurophysiological study in Chinese population. Ann Transl Med. 2020; 8(21):1372.
Chen Chen, Yue Zhang, Hui Wu et al. Clinical and molecular genetic features of cerebrotendinous xanthomatosis patients in Chinese families Metabolic Brain Disease. 2017; 32: 1609-18.
Ohno T, Kobayashi S, Hayashi M, Sakurai M, Kanazawa I. Diphenylpyraline-responsive parkinsonism in cerebrotendinous xanthomatosis: long-term follow up of three patients. J Neurol Sci. 2001;182:95–97.
Lagarde J, Roze E, Apartis E et al. Myoclonus and dystonia in cerebrotendinous xanthomatosis. Mov Disord. 2012, 27:1805–1810.
Sedel F, Baumann N, Turpin JC, Lyon-Caen O, Saudubray JM, Cohen D: Psychiatric manifestations revealing inborn errors of metabolism in adolescents and adults. J Inherit Metab Dis. 2007, 30:631–641.
Chen Q, Liu W, Jiang B, Yu R, Li X, Li H. Fluoxetine-responsive depression in a Chinese cerebrotendinous xanthomatosis. Gen Hosp Psychiatry 2012, 34(578):571–574.
Fraidakis MJ. Psychiatric manifestations in cerebrotendinous xanthomatosis. Transl Psychiatry.2013; 3:e302
Larson A, Weisfeld-Adams JD, Benke TA, Bonnen PE. Cerebrotendinous xanthomatosis presenting with infantile spasms and intellectual disability. JIMD Rep.2017; 35:1–5
Pedroso JL, Pinto WB, Souza PV et al. Early-onset epilepsy as the main neurological manifestation of cerebrotendinous xanthomatosis. Epilepsy Behav. 2012, 24:380–381.
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; 38: 981–982.
De Stefano N, Dotti MT, Mortilla M, Federico A. Magnetic resonance imaging and spectroscopic changes in brains of patients with cerebrotendinous xanthomatosis. Brain. 2001;124(Pt1):121-131.
Gelzo M, Di Taranto MD, Bisecco A et al. A case of Cerebrotendinous Xanthomatosis with spinal cord involvement and without tendon xanthomas: identification of a new mutation of the CYP27A1 gene. Acta Neurol Belg. 2019;24.
Barkhof F, Verrips A, Wesseling P et al. Cerebrotendinous xanthomatosis: the spectrum of imaging findings and the correlation with neuropathologic findings. Radiology 2000; 217:869.
Duell PB, Salen G, Eichler FS et al. Diagnosis, treatment, and clinical outcomes in 43 cases with cerebrotendinous xanthomatosis. J Clin Lipidol 2018; 12:1169.
Skrede S, Björkhem I, Kvittingen EA et al. Demonstration of 26-hydroxylation of C27-steroids in human skin fibroblasts, and a deficiency of this activity in CTX. J Clin Invest. 1986; 78: 729–735.
Mignarri A, Gallus GN, Dotti MT, Federico A. A suspicion index for early diagnosis and treatment of cerebrotendinous xanthomatosis. J Inherit Metab Dis.2014;37(3):421-429.
Stelten BML, van der Knaap MS, Wevers RA, Verrips A. Cerebellar Disease Mimicking Cerebrotendinous Xanthomatosis: Langerhans Cell Histiocytosis. Pediatr Neurol. 2017; 73:98.
Lewis B, Mitchell WD, Marenah CB, Cortese C. Cerebrotendinous xanthomatosis: biochemical response to inhibition of cholesterol synthesis. Br Med J.1983; 287:2122.
Mimura Y, Kuriyama M, Tokimura Y et al. Treatment of cerebrotendinous xanthomatosis with low density lipoprotein (LD L)-apheresis. J Neurol Sci.1993; 114:227–230.
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; 25:185.
Verrips A, Dotti MT, Mignarri A, Stelten BML, Verma S, Federico A. The safety and effectiveness of chenodeoxycholic acid treatment in patients with cerebrotendinous xanthomatosis: two retrospective cohort studies. Neurol Sci. 2020;41(4):943-949.
Martini G, Mignarri A, Ruvio M et al. Long-term bone density evaluation in cerebrotendinous xanthomatosis: evidence of improvement after chenodeoxycholic acid treatment. Calcif Tissue Int. 2013, 92:282–286.
Islam M, Hoggard N, Hadjivassiliou M. Cerebrotendinous Xanthomatosis: diversity of presentation and refining treatment with chenodeoxycholic acid. Cerebellum Ataxias. 2021;28;8(1):5.
Clayton PT, Verrips A, Sistermans E et al. Mutations in the sterol 27-hydroxylase gene (CYP27A) cause hepatitis of infancy as well as cerebrotendinous xanthomatosis. J Inherit Metab Dis. 2002; 25:501–513
Brass EP, Stelten BML, Verrips A. Cerebrotendinous xanthomatosis-associated diarrhea and response to chenodeoxycholic acid treatment. JIMD Rep. 2020;30;56(1):105-111.
Shen CH, Wang ZX. Liver transplantation due to cerebrotendinous xanthomatosis end-stage liver disease. World J Pediatr. 2018;14(4):414-415.
Uygunoglu U, Gunduz A, Menku SF et al. Cerebrotendinous xanthomatosis: the effectiveness of high-dose piracetam for the treatment of cerebellar and sensorial ataxia. Cerebellum 2014; 13:787.
DeBarber AE, Luo J, Star-Weinstock M et al. A blood test for cerebrotendinous xanthomatosis with potential for disease detection in newborns. J Lipid Res 2014;55 (1):146–54.
Hong X, Daiker J, Sadilek M et al. Toward newborn screening of cerebrotendinous xanthomatosis: results of a biomarker research study using 32,000 newborn dried blood spots. Genet Med. 2020;22(10):1606-1612.
Vaz FM, Bootsma AH, Kulik W, Verrips A et al. A newborn screening method for cerebrotendinous xanthomatosis using bile alcohol glucuronides and metabolite ratios. Journal of lipid research 2017; 58 (5):1002–1007.
