{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T12:45:52Z","timestamp":1776689152976,"version":"3.51.2"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,4,27]],"date-time":"2018-04-27T00:00:00Z","timestamp":1524787200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Amicus Therapeutics, Inc"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"published-print":{"date-parts":[[2018,12]]},"DOI":"10.1186\/s13023-018-0813-7","type":"journal-article","created":{"date-parts":[[2018,4,27]],"date-time":"2018-04-27T11:16:35Z","timestamp":1524827795000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Migalastat improves diarrhea in patients with Fabry disease: clinical-biomarker correlations from the phase 3 FACETS trial"],"prefix":"10.1186","volume":"13","author":[{"given":"Raphael","family":"Schiffmann","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel G.","family":"Bichet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Jovanovic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Derralynn A.","family":"Hughes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"Giugliani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulla","family":"Feldt-Rasmussen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suma P.","family":"Shankar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Barisoni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert B.","family":"Colvin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. Charles","family":"Jennette","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fred","family":"Holdbrook","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Mulberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey P.","family":"Castelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nina","family":"Skuban","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jay A.","family":"Barth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen","family":"Nicholls","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2018,4,27]]},"reference":[{"issue":"3","key":"813_CR1","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1001\/jama.281.3.249","volume":"281","author":"PJ Meikle","year":"1999","unstructured":"Meikle PJ, Hopwood JJ, Clague AE, Carey WF. Prevalence of lysosomal storage disorders. JAMA. 1999;281(3):249\u201354.","journal-title":"JAMA"},{"key":"813_CR2","doi-asserted-by":"publisher","unstructured":"Desnick RJ, Ioannou Y, Eng CM. \u03b1-Galactosidase A deficiency: Fabry disease. The online metabolic and molecular bases of inherited disease. 2016; https:\/\/doi.org\/10.1036\/ommbid.181 .","DOI":"10.1036\/ommbid.181"},{"key":"813_CR3","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/1750-1172-5-30","volume":"5","author":"DP Germain","year":"2010","unstructured":"Germain DP. Fabry disease. Orphanet J Rare Dis. 2010;5:30.","journal-title":"Orphanet J Rare Dis"},{"issue":"3","key":"813_CR4","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1111\/cge.12261","volume":"86","author":"M Rigoldi","year":"2014","unstructured":"Rigoldi M, Concolino D, Morrone A, et al. Intrafamilial phenotypic variability in four families with Anderson-Fabry disease. Clin Genet. 2014;86(3):258\u201363.","journal-title":"Clin Genet"},{"issue":"19","key":"813_CR5","doi-asserted-by":"publisher","first-page":"1599","DOI":"10.1212\/WNL.0b013e3181c0d47a","volume":"73","author":"S Messina","year":"2009","unstructured":"Messina S, Tortorella G, Concolino D, et al. Congenital muscular dystrophy with defective alpha-dystroglycan, cerebellar hypoplasia, and epilepsy. Neurology. 2009;73(19):1599\u2013601.","journal-title":"Neurology"},{"issue":"3","key":"813_CR6","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1086\/318809","volume":"68","author":"CM Eng","year":"2001","unstructured":"Eng CM, Banikazemi M, Gordon RE, et al. A phase 1\/2 clinical trial of enzyme replacement in fabry disease: pharmacokinetic, substrate clearance, and safety studies. Am J Hum Genet. 2001;68(3):711\u201322.","journal-title":"Am J Hum Genet"},{"issue":"1","key":"813_CR7","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1073\/pnas.97.1.365","volume":"97","author":"R Schiffmann","year":"2000","unstructured":"Schiffmann R, Murray GJ, Treco D, et al. Infusion of alpha-galactosidase a reduces tissue globotriaosylceramide storage in patients with Fabry disease. Proc Natl Acad Sci U S A. 2000;97(1):365\u201370.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"33","key":"813_CR8","doi-asserted-by":"publisher","first-page":"6009","DOI":"10.2174\/13816128113199990347","volume":"19","author":"P Buda","year":"2013","unstructured":"Buda P, Ksiazyk J, Tylki-Szymanska A. Gastroenterological complications of Anderson-Fabry disease. Curr Pharm Des. 2013;19(33):6009\u201313.","journal-title":"Curr Pharm Des"},{"issue":"3","key":"813_CR9","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1111\/j.1365-2362.2004.01309.x","volume":"34","author":"A Mehta","year":"2004","unstructured":"Mehta A, Ricci R, Widmer U, et al. Fabry disease defined: baseline clinical manifestations of 366 patients in the Fabry outcome survey. Eur J Clin Investig. 2004;34(3):236\u201342.","journal-title":"Eur J Clin Investig"},{"issue":"4","key":"813_CR10","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/j.ymgme.2005.04.009","volume":"85","author":"M Banikazemi","year":"2005","unstructured":"Banikazemi M, Ullman T, Desnick RJ. Gastrointestinal manifestations of Fabry disease: clinical response to enzyme replacement therapy. Mol Genet Metab. 2005;85(4):255\u20139.","journal-title":"Mol Genet Metab"},{"issue":"12","key":"813_CR11","doi-asserted-by":"publisher","first-page":"1447","DOI":"10.1016\/j.cgh.2007.08.012","volume":"5","author":"B Hoffmann","year":"2007","unstructured":"Hoffmann B, Schwarz M, Mehta A, Keshav S. Gastrointestinal symptoms in 342 patients with Fabry disease: prevalence and response to enzyme replacement therapy. Clin Gastroenterol Hepatol. 2007;5(12):1447\u201353.","journal-title":"Clin Gastroenterol Hepatol"},{"issue":"4","key":"813_CR12","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1023\/A:1015511908710","volume":"11","author":"KF Gold","year":"2002","unstructured":"Gold KF, Pastores GM, Botteman MF, et al. Quality of life of patients with Fabry disease. Qual Life Res. 2002;11(4):317\u201327.","journal-title":"Qual Life Res"},{"issue":"4","key":"813_CR13","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1038\/gim.2016.122","volume":"19","author":"ER Benjamin","year":"2017","unstructured":"Benjamin ER, Della Valle MC, Wu X, et al. The validation of pharmacogenetics for the identification of Fabry patients to be treated with migalastat. Genet Med. 2017;19(4):430\u20138.","journal-title":"Genet Med"},{"key":"813_CR14","unstructured":"Galafold [summary of product characteristics]. Buckinghamshire, UK; Amicus Therapeutics UK Ltd: 2017. http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/EPAR_-_Product_Information\/human\/004059\/WC500208434.pdf ."},{"issue":"6","key":"813_CR15","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1056\/NEJMoa1510198","volume":"375","author":"DP Germain","year":"2016","unstructured":"Germain DP, Hughes DA, Nicholls K, et al. Treatment of Fabry's disease with the pharmacologic chaperone migalastat. N Engl J Med. 2016;375(6):545\u201355.","journal-title":"N Engl J Med"},{"issue":"4","key":"813_CR16","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1136\/jmedgenet-2016-104178","volume":"54","author":"DA Hughes","year":"2017","unstructured":"Hughes DA, Nicholls K, Shankar SP, et al. Oral pharmacological chaperone migalastat compared with enzyme replacement therapy in Fabry disease: 18-month results from the randomised phase III ATTRACT study. J Med Genet. 2017;54(4):288\u201396.","journal-title":"J Med Genet"},{"issue":"11","key":"813_CR17","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1007\/s40265-016-0607-y","volume":"76","author":"A Markham","year":"2016","unstructured":"Markham A. Migalastat: first global approval. Drugs. 2016;76(11):1147\u201352.","journal-title":"Drugs"},{"issue":"2","key":"813_CR18","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1007\/BF01535722","volume":"33","author":"J Svedlund","year":"1988","unstructured":"Svedlund J, Sjodin I, Dotevall G. GSRS\u2014a clinical rating scale for gastrointestinal symptoms in patients with irritable bowel syndrome and peptic ulcer disease. Dig Dis Sci. 1988;33(2):129\u201334.","journal-title":"Dig Dis Sci"},{"issue":"7","key":"813_CR19","doi-asserted-by":"publisher","first-page":"816","DOI":"10.5858\/arpa.2011-0350-OA","volume":"136","author":"L Barisoni","year":"2012","unstructured":"Barisoni L, Jennette JC, Colvin R, et al. Novel quantitative method to evaluate globotriaosylceramide inclusions in renal peritubular capillaries by virtual microscopy in patients with Fabry disease. Arch Pathol Lab Med. 2012;136(7):816\u201324.","journal-title":"Arch Pathol Lab Med"},{"issue":"7","key":"813_CR20","doi-asserted-by":"publisher","first-page":"3476","DOI":"10.1021\/ac404000d","volume":"86","author":"M Boutin","year":"2014","unstructured":"Boutin M, Auray-Blais C. Multiplex tandem mass spectrometry analysis of novel plasma lyso-Gb(3)-related analogues in Fabry disease. Anal Chem. 2014;86(7):3476\u201383.","journal-title":"Anal Chem"},{"issue":"Suppl 1","key":"813_CR21","first-page":"S161","volume":"37","author":"ER Benjamin","year":"2014","unstructured":"Benjamin ER, Hamler R, Brignol N, Boyd R, Yu J, Bragat A, et al. Migalastat reduces plasma globotriaosylsphingosine (lyso-Gb3) in Fabry patients: results from the FACETS phase 3 study. J Inherit Metab Dis. 2014;37(Suppl 1):S161.","journal-title":"J Inherit Metab Dis"},{"issue":"1","key":"813_CR22","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.transproceed.2013.09.026","volume":"46","author":"M Sterneck","year":"2014","unstructured":"Sterneck M, Settmacher U, Ganten T, et al. Improvement in gastrointestinal and health-related quality of life outcomes after conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in liver transplant recipients. Transplant Proc. 2014;46(1):234\u201340.","journal-title":"Transplant Proc"},{"key":"813_CR23","doi-asserted-by":"publisher","first-page":"205","DOI":"10.2147\/CEG.S81922","volume":"8","author":"B Manger","year":"2015","unstructured":"Manger B, Hiepe F, Schneider M, et al. Impact of switching from mycophenolate mofetil to enteric-coated mycophenolate sodium on gastrointestinal side effects in patients with autoimmune disease: a phase III, open-label, single-arm, multicenter study. Clin Exp Gastroenterol. 2015;8:205\u201313.","journal-title":"Clin Exp Gastroenterol"},{"issue":"9","key":"813_CR24","doi-asserted-by":"publisher","first-page":"1290","DOI":"10.1097\/01.tp.0000209411.66790.b3","volume":"81","author":"L Chan","year":"2006","unstructured":"Chan L, Mulgaonkar S, Walker R, Arns W, Ambuhl P, Schiavelli R. Patient-reported gastrointestinal symptom burden and health-related quality of life following conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium. Transplantation. 2006;81(9):1290\u20137.","journal-title":"Transplantation"},{"issue":"2","key":"813_CR25","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1093\/biostatistics\/4.2.223","volume":"4","author":"X Xu","year":"2003","unstructured":"Xu X, Tian L, Wei LJ. Combining dependent tests for linkage or association across multiple phenotypic traits. Biostatistics. 2003;4(2):223\u20139.","journal-title":"Biostatistics"},{"issue":"33","key":"813_CR26","doi-asserted-by":"publisher","first-page":"6014","DOI":"10.2174\/13816128113199990387","volume":"19","author":"A Tuttolomondo","year":"2013","unstructured":"Tuttolomondo A, Pecoraro R, Simonetta I, et al. Neurological complications of Anderson-Fabry disease. Curr Pharmacy Des. 2013;19(33):6014\u201330.","journal-title":"Curr Pharmacy Des."},{"issue":"33","key":"813_CR27","doi-asserted-by":"publisher","first-page":"5974","DOI":"10.2174\/13816128113199990352","volume":"19","author":"A Tuttolomondo","year":"2013","unstructured":"Tuttolomondo A, Pecoraro R, Simonetta I, et al. Anderson-Fabry disease: a multiorgan disease. Curr Pharmacy Des. 2013;19(33):5974\u201396.","journal-title":"Curr Pharmacy Des"},{"key":"813_CR28","volume-title":"Fabry disease: perspectives from 5 years of FOS","author":"S Keshav","year":"2006","unstructured":"Keshav S. Gastrointestinal manifestations of Fabry disease. In: Mehta A, Beck M, Sunder-Plassmann G, editors. Fabry disease: perspectives from 5 years of FOS. Oxford: Oxford PharmaGenesis; 2006."},{"issue":"5 Pt 1","key":"813_CR29","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1016\/S0016-5085(82)80262-X","volume":"82","author":"BD O'Brien","year":"1982","unstructured":"O'Brien BD, Shnitka TK, McDougall R, et al. Pathophysiologic and ultrastructural basis for intestinal symptoms in Fabry\u2019s disease. Gastroenterology. 1982;82(5 Pt 1):957\u201362.","journal-title":"Gastroenterology"},{"issue":"1","key":"813_CR30","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1111\/cge.12673","volume":"89","author":"J Politei","year":"2016","unstructured":"Politei J, Thurberg BL, Wallace E, et al. Gastrointestinal involvement in Fabry disease. So important, yet often neglected. Clin Genet. 2016;89(1):5\u20139.","journal-title":"Clin Genet"},{"issue":"9","key":"813_CR31","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1080\/00365520310004209","volume":"38","author":"IK Wiklund","year":"2003","unstructured":"Wiklund IK, Fullerton S, Hawkey CJ, et al. An irritable bowel syndrome-specific symptom questionnaire: development and validation. Scand J Gastroenterol. 2003;38(9):947\u201354.","journal-title":"Scand J Gastroenterol"},{"key":"813_CR32","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/1477-7525-6-12","volume":"6","author":"KR Kulich","year":"2008","unstructured":"Kulich KR, Madisch A, Pacini F, et al. Reliability and validity of the gastrointestinal symptom rating scale (GSRS) and quality of life in reflux and dyspepsia (QOLRAD) questionnaire in dyspepsia: a six-country study. Health Qual Life Outcomes. 2008;6:12.","journal-title":"Health Qual Life Outcomes"},{"issue":"1","key":"813_CR33","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1023\/A:1008841022998","volume":"7","author":"DA Revicki","year":"1998","unstructured":"Revicki DA, Wood M, Wiklund I, Crawley J. Reliability and validity of the gastrointestinal symptom rating scale in patients with gastroesophageal reflux disease. Qual Life Res. 1998;7(1):75\u201383.","journal-title":"Qual Life Res"}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-018-0813-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13023-018-0813-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-018-0813-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,1]],"date-time":"2020-11-01T09:54:20Z","timestamp":1604224460000},"score":1,"resource":{"primary":{"URL":"https:\/\/ojrd.biomedcentral.com\/articles\/10.1186\/s13023-018-0813-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,27]]},"references-count":33,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,12]]}},"alternative-id":["813"],"URL":"https:\/\/doi.org\/10.1186\/s13023-018-0813-7","relation":{},"ISSN":["1750-1172"],"issn-type":[{"value":"1750-1172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,27]]},"assertion":[{"value":"29 November 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 April 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 April 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Written consent to participate in the study was obtained from all patients. The study was approved by the institutional review board or ethics committee at each participating center and was conducted in accordance with the International Conference on Harmonisation Good Clinical Practice guidelines and the principles of the Declaration of Helsinki.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"RS has served as a consultant for and received research funding from Protalix Biotherapeutics and Amicus. DGB has received research funding, serves as a consultant, and is on the speaker\u2019s bureau for Amicus and Genzyme, and has received research funding from Shire. AJ has received advisory honoraria and speaker\u2019s fees from Shire, Amicus, Biomarin, and Genzyme. DAH has served as a consultant for and received research funding and honoraria from Amicus, Shire, Genzyme, Protalix, and Actelion. RG has received honoraria from Amicus, Biomarin, Genzyme, and Shire. UFR reports other support from Amicus during the conduct of the study, grant support and speaker\u2019s honoraria from Amicus, Genzyme, and Shire HGT outside the submitted work, and research funding from Novo Nordisk Research Foundation. SPS reports grants and non-financial support from Amicus during the conduct of the study. LB has served as a consultant for Protalix. RBC has served as a consultant for Amicus and has received grants from the National Institutes of Health. JCJ does not have anything to disclose. KN has served as an advisor for Amicus, Shire HGT, and Genzyme, has received research support from Amicus and Shire HGT, and has received travel support from Genzyme. FH, AM, JPC, NS, and JAB are employees of and hold stock in Amicus.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Publisher\u2019s Note"}}],"article-number":"68"}}