medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLCmedgen-194Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHОксистеролы в дифференциальной диагностике лизосомных болезней накопленияDifferential diagnostics of lysosomal storage disorders using oxysterol assayПрошляковаТ. Ю.ProshlyakovaT. Y.t.proshlyakova@mail.ruБайдаковаГ. В.BaydakovaG. V.noemail@neicon.ruКаменецЕ. А.KamenetsE. A.noemail@neicon.ruМихайловаС. В.MikhailovaS. V.noemail@neicon.ruМалаховаВ. А.MalakhovaV. A.noemail@neicon.ruЗахароваЕ. Ю.ZakharovaE. Y.noemail@neicon.ruФГБНУ «Медико-генетический научный центр»РоссияResearch Centre for Medical GeneticsRussian FederationФГБУ «Российская детская клиническая больница» Минздрава РоссииРоссияRussian Children’s Clinical HospitalRussian Federation20162601201715123741Copyright © Прошлякова Т.Ю., Байдакова Г.В., Каменец Е.А., Михайлова С.В., Малахова В.А., Захарова Е.Ю., 20172017Прошлякова Т.Ю., Байдакова Г.В., Каменец Е.А., Михайлова С.В., Малахова В.А., Захарова Е.Ю.Proshlyakova T.Y., Baydakova G.V., Kamenets E.A., Mikhailova S.V., Malakhova V.A., Zakharova E.Y.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medgen-journal.ru/jour/article/view/194

Липидозы - группа наследственных лизосомных заболеваний, характеризующаяся накоплением в тканях сложных липидов. Целью данного исследования являлась оценка концентрации оксистеролов: холестан-3b,5a,6b-триола (C-триол) и 7-кетохолестерина (7-KC) при 4 лизосомных болезнях из группы липидозов и у гетерозиготных носителей болезни Ниманна-Пика типа С и Ниманна-Пика типа А/В. Показано повышение концентрации холестан-3b,5a,6b-триола при болезни Ниманна-Пика типа С, Ниманна-Пика типа А/В и дефиците лизосомной кислой липазы. Не выявлено значимых изменений этого метаболита у пациентов с болезнью Гоше. Показано повышение концентрации С-триола у гетерозиготных носителей болезни Ниманна-Пика типа С. Выявлено диагностически значимое соотношение холестан-3b,5a,6b-триол/7-кетохолестерин, позволяющие улучшить лабораторную дифференциальную диагностику этих заболеваний. Определение концентрации оксистеролов можно применять в качестве одного из биохимических тестов для селективного скрининга групп риска на лизосомные болезни накопления.

Lipidoses is a group of inherited lysosomal diseases, characterized by accumulation of complex lipids in the tissues. The aim of this study was to evaluate the levels of oxysterols: cholestan-3b,5a,6b-triol (C-triol) and 7-ketocholesterol (7-KC) at four lysosomal diseases from the lipidoses group and in heterozygous carriers of Niemann-Pick (NP) type C and Niemann-Pick type A/B diseases. Increased levels of cholestan-3b,5a,6b-triol were found at NP-C, NP-A/B, and deficiency of lysosomal acid lipase (LAL-D). The level of C-triol was not increased in Gousher’s syndrome patients. An increased average concentration of cholestan-3b,5a,6b-triol was also revealed in heterozygous carriers of Niemann-Pick type C disease. A diagnostically significant cholestan-3b,5a,6b-triol/7-ketocholesterol ratio was proposed that can improve laboratory differential diagnostics of these diseases. The oxysterol assay can be used as a biochemical technique for selective screening of the risk groups for these diseases.

биохимические маркерыоксистеролыC-триолЛБННП-А/B/Cнедостаточность лизосомной кислой липазыbiochemical markersoxysterolsС-triolLSDNP-A/B/CLAL-DReferencesПрошлякова Т.Ю., Байдакова Г.В., Букина Т.М., Михайлова С.В., Ильина Е.С., Руденская Г.Е., Клюшников С.А., Малахова В.А., Захарова Е.Ю. Биохимические маркеры при болезни Ниманна-Пика типа С. Мед. Ген. 2015; (8): 3-6.Прошлякова Т.Ю., Байдакова Г.В., Букина Т.М., Михайлова С.В., Ильина Е.С., Руденская Г.Е., Клюшников С.А., Малахова В.А., Захарова Е.Ю. Биохимические маркеры при болезни Ниманна-Пика типа С. Мед. Ген. 2015; (8): 3-6.Boenzi S, Deodato F, Taurisano R, Martinelli D, Verrigni D. A new simple and rapid LC-ESI-MS/MS method for quantification of plasma oxysterols as dimethylaminobutyrate esters. Its successful use for the diagnosis of Niemann-Pick type C disease. Clin. Chia. Acta. 2014; (437): 93-100.Boenzi S, Deodato F, Taurisano R, Martinelli D, Verrigni D. A new simple and rapid LC-ESI-MS/MS method for quantification of plasma oxysterols as dimethylaminobutyrate esters. Its successful use for the diagnosis of Niemann-Pick type C disease. Clin. Chia. Acta. 2014; (437): 93-100.Boenzi S, Deodato F, Taurisano R, Goffredo BM, Rizzo C, Dionisi-Vici C. Evaluation of plasma cholestane-3b,5a,6b-triol and 7-ketocholesterol in inherited disorders related to cholesterol metabolism. J. Lip. Res. 2016; (57): 361-367.Boenzi S, Deodato F, Taurisano R, Goffredo BM, Rizzo C, Dionisi-Vici C. Evaluation of plasma cholestane-3b,5a,6b-triol and 7-ketocholesterol in inherited disorders related to cholesterol metabolism. J. Lip. Res. 2016; (57): 361-367.Carstea ED, Morris JA, Coleman KG Niemann-Pick C1 disease gene: homology to mediators of cholesterol Homeostasis. Science. 1997; (277): 228-231.Carstea ED, Morris JA, Coleman KG Niemann-Pick C1 disease gene: homology to mediators of cholesterol Homeostasis. Science. 1997; (277): 228-231.Clarke JTR. A Clinical Guide to Inherited Metabolic Diseases. Camb. Univ. Press. 2005: 358.Clarke JTR. A Clinical Guide to Inherited Metabolic Diseases. Camb. Univ. Press. 2005: 358.Forbes DP, Scherrer DE, Lanier MH, Langmade SJ. Cholesterol oxidation products are sensitive and specific bloodbased biomarkers for Niemann-Pick C1 disease. Sci Transl. Med. 2010 November 3; (2): 56-81Forbes DP, Scherrer DE, Lanier MH, Langmade SJ. Cholesterol oxidation products are sensitive and specific bloodbased biomarkers for Niemann-Pick C1 disease. Sci Transl. Med. 2010 November 3; (2): 56-81Fuller M, Meikle P, Hopwood J. Epidemiology of lysosomal storage diseases: an overview. Oxford PharmaGenesis. 2006; (2)Fuller M, Meikle P, Hopwood J. Epidemiology of lysosomal storage diseases: an overview. Oxford PharmaGenesis. 2006; (2)Helmschrodt C, Becker S, Schroter J, Hecht M. Fast LC-MS/MS analysis of free oxysterols derived from reactive oxygen species in human plasma and corotid plaque. Clin. Chia. Acta. 2013; (425): 3-8.Helmschrodt C, Becker S, Schroter J, Hecht M. Fast LC-MS/MS analysis of free oxysterols derived from reactive oxygen species in human plasma and corotid plaque. Clin. Chia. Acta. 2013; (425): 3-8.Helmschrodt C. Becker S, Thiery J, Ceglarec U. Prenalytical standartization for reactive oxygen species derived oxysterol analisis in human plasma by liquid chromatography-tandem mass spectrometry. Biochem. Biophys. Res. Commun. 2014Helmschrodt C. Becker S, Thiery J, Ceglarec U. Prenalytical standartization for reactive oxygen species derived oxysterol analisis in human plasma by liquid chromatography-tandem mass spectrometry. Biochem. Biophys. Res. Commun. 2014Jiang X, Sidhu R, Porter FD. A sensitive and specific LC-MS/MS method for rapid diagnosis of Niemann-Pick C1 disease from human plasma. J. Lipid. Res. 2011; (52): 1435-1445.Jiang X, Sidhu R, Porter FD. A sensitive and specific LC-MS/MS method for rapid diagnosis of Niemann-Pick C1 disease from human plasma. J. Lipid. Res. 2011; (52): 1435-1445.Kant R. van der, Zondervan I, Janssen L, Neefjes J. Cholesterol-binding molecules MLN64 and ORP1L mark distinct late endosomes with transporters ABCA3 and NPC1. J. Lipid Res. 2013; (54): 2153-2165.Kant R. van der, Zondervan I, Janssen L, Neefjes J. Cholesterol-binding molecules MLN64 and ORP1L mark distinct late endosomes with transporters ABCA3 and NPC1. J. Lipid Res. 2013; (54): 2153-2165.Klinke G, M. Rohrbach, R. Giugliani, P. Burda, M.R. Baumgartner, C. Tran, M. Gautschi, D.Mathis, M. Hersberger, LC-MS/MS based assay and reference intervals in children and adolescents for oxysterols elevated in Niemann-Pick diseases. Clin. Biochem. 2015; (48): 596-602.Klinke G, M. Rohrbach, R. Giugliani, P. Burda, M.R. Baumgartner, C. Tran, M. Gautschi, D.Mathis, M. Hersberger, LC-MS/MS based assay and reference intervals in children and adolescents for oxysterols elevated in Niemann-Pick diseases. Clin. Biochem. 2015; (48): 596-602.Krasnopolskaya K.D., Mirenburg T.V., Aronovich E.L. Diagnosis and prevention of lysosomal storage diseases in Russia. Inherit Metab. Dis. 1993; (16): 994-1002.Krasnopolskaya K.D., Mirenburg T.V., Aronovich E.L. Diagnosis and prevention of lysosomal storage diseases in Russia. Inherit Metab. Dis. 1993; (16): 994-1002.Maxfield F, Wustner D, Analysis of cholesterol trafficking with fluorescent probes. Meth. Cell Biol. 2012; (108): 367-393.Maxfield F, Wustner D, Analysis of cholesterol trafficking with fluorescent probes. Meth. Cell Biol. 2012; (108): 367-393.Sechi A, Dardis A, Zampieri S, Rabacchi C, Zanoni P, Calandra S, G. De Maglio, Pizzolitto S, Maruotti V, A. DiMuzio, Platt F, Bembi B. Effects of miglustat treatment in a patient affected by an atypical form of Tangier disease. Orphanet J. Rare Dis. 2014; (9): 143.Sechi A, Dardis A, Zampieri S, Rabacchi C, Zanoni P, Calandra S, G. De Maglio, Pizzolitto S, Maruotti V, A. DiMuzio, Platt F, Bembi B. Effects of miglustat treatment in a patient affected by an atypical form of Tangier disease. Orphanet J. Rare Dis. 2014; (9): 143.Walterfang M, Velakoulis D, Niemann-Pick disease type C in adulthood - a psychiatric and neurological disorder, Eur. Psychiatr. Rev. 2010; (3): 16-20.Walterfang M, Velakoulis D, Niemann-Pick disease type C in adulthood - a psychiatric and neurological disorder, Eur. Psychiatr. Rev. 2010; (3): 16-20.Zhang J, Coleman T, Langmade SJ, Scherrer DE, Lane L, Lanier MH, Feng C, Sands MS, Schaffer JE, Semenkovich CF, Ory DS, Niemann-Pick C1 protects against therosclerosis in mice via regulation of macrophage intracellular cholesterol trafficking. J. Clin. Invest. 2008; (118): 2281-2290.Zhang J, Coleman T, Langmade SJ, Scherrer DE, Lane L, Lanier MH, Feng C, Sands MS, Schaffer JE, Semenkovich CF, Ory DS, Niemann-Pick C1 protects against therosclerosis in mice via regulation of macrophage intracellular cholesterol trafficking. J. Clin. Invest. 2008; (118): 2281-2290.

The authors declare that there are no conflicts of interest present.