{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:54:15Z","timestamp":1790679255361,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,9,30]],"date-time":"2019-09-30T00:00:00Z","timestamp":1569801600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Fabry disease (FD) is a rare X\u2010linked lysosomal storage disorder caused by \u03b1\u2010galactosidase A (\u03b1\u2010Gal A) deficiency. The progressive accumulation of globotriaosylceramide results in life\u2010threatening complications, including renal, cardiac, and cerebrovascular diseases. The pharmacological chaperone migalastat was recently approved as an alternative to enzyme replacement therapy in patients with amenable mutations. In this article, we investigate the proportion of amenable mutations, related to phenotype, in a population of adult patients with FD in Switzerland. This study included 170 adult patients (n = 64 males) from 46 independent pedigrees with 39 different identified mutations over the last 59\u2009years. Overall, 68% had the classic phenotype and 48% fulfilled the current amenability criteria. Migalastat was stopped in 2\/11 (18%) patients: the only male classic patient, because of lack of efficacy based on lyso\u2010Gb3 levels, and one patient with a benign variant. In males, the achieved enzyme activities in peripheral leucocytes under migalastat treatment differed from the activities in HEK\u2010cells after incubation with migalastat (eg, 33% in PL vs 41% HEK\u2010cells for p.F113L; 43% in leucocytes vs 36% in HEK\u2010cells for p.N215S, 24\u201030% in leucocytes vs 96% in HEK\u2010cells for S238N). In this national cohort, we found a relatively high proportion of patients with amenable <jats:italic>GLA<\/jats:italic> mutations, which, however, had heterogeneous extent of amenability: the higher the residual \u03b1\u2010Gal A activity, the higher the chaperone effect. Further studies are required to investigate the long\u2010term benefits of migalastat therapy depending on the achieved enzyme activities in different amenable mutations.<\/jats:p>","DOI":"10.1002\/jimd.12167","type":"journal-article","created":{"date-parts":[[2019,8,26]],"date-time":"2019-08-26T15:04:42Z","timestamp":1566831882000},"page":"326-333","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Fabry disease genotype, phenotype, and migalastat amenability: Insights from a national cohort"],"prefix":"10.1002","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4119-5516","authenticated-orcid":false,"given":"Albina","family":"Nowak","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Clinical Nutrition University Hospital Zurich and University of Zurich  Zurich Switzerland"},{"name":"Department of Internal Medicine Psychiatry University Hospital Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uyen","family":"Huynh\u2010Do","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension University Hospital Bern and University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre\u2010Alexandre","family":"Krayenbuehl","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Linth Hospital  Uznach Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7826-3984","authenticated-orcid":false,"given":"Felix","family":"Beuschlein","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Clinical Nutrition University Hospital Zurich and University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael","family":"Schiffmann","sequence":"additional","affiliation":[{"name":"Institute of Metabolic Disease, Baylor Scott &amp; White Research Institute  Dallas Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Barbey","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine Lausanne University Hospital and University of Lausanne  Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,9,30]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1006\/rwgn.2001.0443"},{"key":"e_1_2_9_3_1","article-title":"Characterization of Classical and Nonclassical Fabry Disease: A Multicenter Study","volume":"28","author":"Arends M","year":"2016","journal-title":"J Am Soc Nephrol"},{"key":"e_1_2_9_4_1","article-title":"Plasma LysoGb3: A useful biomarker for the diagnosis and treatment of Fabry disease heterozygotes","volume":"120","author":"Nowak A","year":"2016","journal-title":"Mol Genet Metab"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfp031"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12613"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200107053450102"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2014-102797"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.285.21.2743"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1510198"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2016.122"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1086\/376608"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-017-1779-6"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21530"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-017-0098-3"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1086\/504601"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-7-91"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2013.01.009"},{"key":"e_1_2_9_19_1","article-title":"Oral chaperone therapy migalastat for treating Fabry disease: enzymatic response and serum biomarker changes after one year","volume":"105","author":"Muntze J","year":"2018","journal-title":"Clin Pharmacol Ther"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2012.00002"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2007.06.062"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2016.55"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/1479-7364-2-5-297"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2003.00160.x"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199508033330504"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199102073240607"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2017-105080"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.12167","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jimd.12167","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.12167","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T03:20:33Z","timestamp":1693365633000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jimd.12167"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,30]]},"references-count":26,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,3]]}},"alternative-id":["10.1002\/jimd.12167"],"URL":"https:\/\/doi.org\/10.1002\/jimd.12167","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,30]]},"assertion":[{"value":"2019-04-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-08-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-09-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}