{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:38:04Z","timestamp":1790872684682,"version":"4.1.0"},"reference-count":51,"publisher":"BMJ","issue":"4","funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["BMBF 01EO1504, MO2"],"award-info":[{"award-number":["BMBF 01EO1504, MO2"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2016,3,3]]},"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>The severity of Fabry disease is dependent on the type of mutation in the \u03b1-galactosidase A (AgalA) encoding gene (GLA). This study focused on the impact of the GLA haplotype D313Y on long-term organ involvement and function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting and participants<\/jats:title>\n                    <jats:p>In this monocentric study, all participants presenting with the D313Y haplotype between 2001 and 2015 were comprehensively clinically investigated at baseline and during a 4-year follow-up if available. Five females and one male were included.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Primary and secondary outcome measures<\/jats:title>\n                    <jats:p>Cardiac, nephrological, neurological, laboratory and quality of life data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      AgalA enzyme activity in leucocytes (0.3\u00b10.9\u2005nmol\/min\/mg protein (mean\u00b1SD)) and serum lyso-Gb3 (0.6\u00b10.3\u2005ng\/mL at baseline) were in normal range in all patients. Cardiac morphology and function were normal (left-ventricular (LV) ejection fraction 66\u00b18%; interventricular septum 7.7\u00b11.4\u2005mm; LV posterior wall 7.5\u00b11.4\u2005mm; normalised LV mass in MRI 52\u00b19\u2005g\/m\n                      <jats:sup>2<\/jats:sup>\n                      ; LV global longitudinal strain \u221221.6\u00b11.9%) and there were no signs of myocardial fibrosis in cardiac MRI. Cardiospecific biomarkers were also in normal range. Renal function was not impaired (estimated glomerular filtration rate MDRD 103\u00b115\u2005mL\/min; serum-creatinine 0.75\u00b10.07\u2005mg\/dL; cystatin-c 0.71\u00b10.12\u2005mg\/L). One female patient (also carrying a Factor V Leiden mutation) had a transitory ischaemic attack. One patient showed white matter lesions in brain MRI, but none had Fabry-associated pain attacks, pain crises, evoked pain or permanent pain. Health-related quality of life analysis revealed a reduction in individual well-being. At long-term follow-up after 4\u2005years, no significant change was seen in any parameter.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The results of the current study suggest that the D313Y genotype does not lead to severe organ manifestations as seen in genotypes known to be causal for classical FD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2015-010422","type":"journal-article","created":{"date-parts":[[2016,4,8]],"date-time":"2016-04-08T23:37:37Z","timestamp":1460158657000},"page":"e010422","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":45,"title":["Organ manifestations and long-term outcome of Fabry disease in patients with the GLA haplotype D313Y"],"prefix":"10.1136","volume":"6","author":[{"given":"Daniel","family":"Oder","sequence":"first","affiliation":[{"name":"Department of Internal Medicine I and Comprehensive Heart Failure Center (CHFC), University Hospital W\u00fcrzburg, W\u00fcrzburg, Germany"},{"name":"Fabry Center for Interdisciplinary Therapy (FAZIT), University Hospital W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurcan","family":"\u00dc\u00e7eyler","sequence":"additional","affiliation":[{"name":"Fabry Center for Interdisciplinary Therapy (FAZIT), University Hospital W\u00fcrzburg, W\u00fcrzburg, Germany"},{"name":"Department of Neurology, University Hospital W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I and Comprehensive Heart Failure Center (CHFC), University Hospital W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I and Comprehensive Heart Failure Center (CHFC), University Hospital W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Petritsch","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Interventional Radiology, University Hospital W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Sommer","sequence":"additional","affiliation":[{"name":"Fabry Center for Interdisciplinary Therapy (FAZIT), University Hospital W\u00fcrzburg, W\u00fcrzburg, Germany"},{"name":"Department of Neurology, University Hospital W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Ertl","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I and Comprehensive Heart Failure Center (CHFC), University Hospital W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Wanner","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I and Comprehensive Heart Failure Center (CHFC), University Hospital W\u00fcrzburg, W\u00fcrzburg, Germany"},{"name":"Fabry Center for Interdisciplinary Therapy (FAZIT), University Hospital W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Nordbeck","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I and Comprehensive Heart Failure Center (CHFC), University Hospital W\u00fcrzburg, W\u00fcrzburg, Germany"},{"name":"Fabry Center for Interdisciplinary Therapy (FAZIT), University Hospital W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2016,4,8]]},"reference":[{"key":"2025121509142483000_6.4.e010422.1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM196705252762101"},{"key":"2025121509142483000_6.4.e010422.2","doi-asserted-by":"publisher","DOI":"10.1126\/science.167.3922.1268"},{"key":"2025121509142483000_6.4.e010422.3","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-138-4-200302180-00014"},{"key":"2025121509142483000_6.4.e010422.4","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-5-30"},{"key":"2025121509142483000_6.4.e010422.5","doi-asserted-by":"crossref","first-page":"5974","DOI":"10.2174\/13816128113199990352","article-title":"Anderson-Fabry disease: a multiorgan disease","volume":"19","author":"Tuttolomondo","year":"2013","journal-title":"Curr Pharm Des"},{"key":"2025121509142483000_6.4.e010422.6","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.38.11.769"},{"key":"2025121509142483000_6.4.e010422.7","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.38.11.750"},{"key":"2025121509142483000_6.4.e010422.8","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1097\/AJP.0000000000000041","article-title":"Characterization of pain in fabry disease","volume":"30","author":"Uceyler","year":"2014","journal-title":"Clin J Pain"},{"key":"2025121509142483000_6.4.e010422.9","doi-asserted-by":"publisher","DOI":"10.2174\/13816128113199990387"},{"key":"2025121509142483000_6.4.e010422.10","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)67635-0"},{"key":"2025121509142483000_6.4.e010422.11","doi-asserted-by":"crossref","first-page":"473","DOI":"10.2174\/138161282104141204142643","article-title":"The Fabry cardiomyopathy\u2014diagnostic approach and current treatment","volume":"21","author":"Weidemann","year":"2015","journal-title":"Curr Pharm Des"},{"key":"2025121509142483000_6.4.e010422.12","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehm153"},{"key":"2025121509142483000_6.4.e010422.13","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfp031"},{"key":"2025121509142483000_6.4.e010422.14","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2008.065904"},{"key":"2025121509142483000_6.4.e010422.15","doi-asserted-by":"publisher","DOI":"10.1038\/nature11632"},{"key":"2025121509142483000_6.4.e010422.16","unstructured":"accessed 19th October 2015). http:\/\/fabry-database.org"},{"key":"2025121509142483000_6.4.e010422.17","doi-asserted-by":"publisher","DOI":"10.1016\/S1096-7192(03)00136-7"},{"key":"2025121509142483000_6.4.e010422.18","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10275"},{"key":"2025121509142483000_6.4.e010422.19","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0055565"},{"key":"2025121509142483000_6.4.e010422.20","first-page":"99","article-title":"Lyso-Gb3 Indicates that the Alpha-Galactosidase A Mutation D313Y is not Clinically Relevant for Fabry Disease","volume":"7","author":"Niemann","year":"2013","journal-title":"JIMD Rep"},{"key":"2025121509142483000_6.4.e010422.21","doi-asserted-by":"publisher","DOI":"10.1093\/ehjci\/jev014"},{"key":"2025121509142483000_6.4.e010422.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.echo.2014.10.003"},{"key":"2025121509142483000_6.4.e010422.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.echo.2008.10.006"},{"key":"2025121509142483000_6.4.e010422.24","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/eht098"},{"key":"2025121509142483000_6.4.e010422.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2006.01.041"},{"key":"2025121509142483000_6.4.e010422.26","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181e0f7b3"},{"key":"2025121509142483000_6.4.e010422.27","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2005.01260.x"},{"key":"2025121509142483000_6.4.e010422.28","doi-asserted-by":"publisher","DOI":"10.2214\/ajr.149.2.351"},{"key":"2025121509142483000_6.4.e010422.29","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0712309105"},{"key":"2025121509142483000_6.4.e010422.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2010.03.020"},{"key":"2025121509142483000_6.4.e010422.31","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.113.000249"},{"key":"2025121509142483000_6.4.e010422.32","doi-asserted-by":"publisher","DOI":"10.1097\/00005650-199205001-00025"},{"key":"2025121509142483000_6.4.e010422.33","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.03890609"},{"key":"2025121509142483000_6.4.e010422.34","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e3181f13a4a"},{"key":"2025121509142483000_6.4.e010422.35","unstructured":"Ware J Jr , Kosinski M , Keller SD . SF-36 physical and mental health summary scales, a user's manual. Booston, MA: The Health Institute , 1994."},{"key":"2025121509142483000_6.4.e010422.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2010.07.026"},{"key":"2025121509142483000_6.4.e010422.37","first-page":"1186","article-title":"Nature and frequency of mutations in the alpha-galactosidase A gene that cause Fabry disease","volume":"53","author":"Eng","year":"1993","journal-title":"Am J Hum Genet"},{"key":"2025121509142483000_6.4.e010422.38","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001333"},{"key":"2025121509142483000_6.4.e010422.39","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1186\/s13023-014-0178-5","article-title":"Cryptogenic stroke and small fiber neuropathy of unknown etiology in patients with alpha-galactosidase A -10T genotype","volume":"9","author":"Schelleckes","year":"2014","journal-title":"Orphanet J Rare Dis"},{"key":"2025121509142483000_6.4.e010422.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2014.09.018"},{"key":"2025121509142483000_6.4.e010422.41","doi-asserted-by":"crossref","unstructured":"Germain DP . A new phenotype of Fabry disease with intermediate severity between the classical form and the cardiac variant. Contrib Nephrol 2001(136):234\u201340. doi:10.1159\/000060194","DOI":"10.1159\/000060194"},{"key":"2025121509142483000_6.4.e010422.42","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.109.862920"},{"key":"2025121509142483000_6.4.e010422.43","first-page":"S113","article-title":"The N215S mutation results in a distinct subtype of Fabry disease","volume":"114","author":"Thomas","year":"2015","journal-title":"Mol Genet Metab"},{"key":"2025121509142483000_6.4.e010422.44","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21074"},{"key":"2025121509142483000_6.4.e010422.45","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.02490607"},{"key":"2025121509142483000_6.4.e010422.46","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-009-1055-6"},{"key":"2025121509142483000_6.4.e010422.47","doi-asserted-by":"publisher","DOI":"10.1159\/000085709"},{"key":"2025121509142483000_6.4.e010422.48","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.ymgme.2013.03.008","article-title":"Fabry patients\u2019 experiences with the timing of diagnosis relevant for the discussion on newborn screening","volume":"109","author":"Bouwman","year":"2013","journal-title":"Mol Genet Metab"},{"key":"2025121509142483000_6.4.e010422.49","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000124671.61963.1E"},{"key":"2025121509142483000_6.4.e010422.50","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfl528"},{"key":"2025121509142483000_6.4.e010422.51","doi-asserted-by":"publisher","DOI":"10.1086\/504601"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2015-010422","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T17:14:37Z","timestamp":1765818877000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2015-010422"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,4]]},"references-count":51,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2016,4,8]]},"published-print":{"date-parts":[[2016,4]]}},"alternative-id":["10.1136\/bmjopen-2015-010422"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2015-010422","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,4]]}}}