{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:05:36Z","timestamp":1791993936923,"version":"4.4.0"},"reference-count":61,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,5,12]],"date-time":"2020-05-12T00:00:00Z","timestamp":1589241600000},"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":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>The identification of pathogenic <jats:italic>GLA<\/jats:italic> variants plays a central role in the establishment of a definite Fabry disease (FD) diagnosis. We aimed to review and interpret the published data on the p.Asp313Tyr (p.D313Y) variant pathogenicity and clinical relevance.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>We performed a systematic review of peer\u2010reviewed publications and case\u2010reports on individuals and populations harbouring the p.Asp313Tyr variant.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>Overall, 35 studies were included in this review. We collected data regarding the clinical manifestations, alpha\u2010galactosidase A enzyme activity, levels of the biomarkers globotriaosylceramide (Gb<jats:sub>3<\/jats:sub>) and sphingosine\u2010globotriaosylceramide (lyso\u2010Gb<jats:sub>3<\/jats:sub>) and histological findings of p.Asp313Tyr carriers. The prevalence of p.Asp313Tyr in populations at risk for FD (kidney, heart, neurologic disorders, or symptomatic populations) was calculated. We found high residual enzyme activity, low frequency of clinical features specific for FD, non\u2010elevated lysoGb<jats:sub>3<\/jats:sub>\/Gb<jats:sub>3<\/jats:sub> concentrations and lack of intracellular Gb<jats:sub>3<\/jats:sub> accumulation in biopsies in the p.Asp313Tyr carriers. The prevalence of the variant in populations at risk for FD was comparable to the reported frequency in the general population. A possible higher frequency was only observed in neurologic disorders.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>p.Asp313Tyr can be classified as neutral or variant of unknown significance. Further investigations will be helpful to clarify a possible association between the variant and manifestations in the brain vessels.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jimd.12240","type":"journal-article","created":{"date-parts":[[2020,4,4]],"date-time":"2020-04-04T09:03:22Z","timestamp":1585991002000},"page":"922-933","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Is the alpha\u2010galactosidase A variant <scp>p.Asp313Tyr<\/scp> (<scp>p.D313Y<\/scp>) pathogenic for Fabry disease? A systematic review"],"prefix":"10.1002","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7313-8391","authenticated-orcid":false,"given":"Grigoris","family":"Effraimidis","sequence":"first","affiliation":[{"name":"Department of Medical Endocrinology and Metabolism Copenhagen University Hospital Rigshospitalet  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c5se K.","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"Department of Medical Endocrinology and Metabolism Copenhagen University Hospital Rigshospitalet  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henning","family":"Bundgaard","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Capital Region's Unit of Inherited Cardiac Diseases, Faculty of Health and Medical Sciences Copenhagen University Hospital Rigshospitalet  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f8ren S.","family":"S\u00f8rensen","sequence":"additional","affiliation":[{"name":"Department of Nephrology Copenhagen University Hospital Rigshospitalet  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulla","family":"Feldt\u2010Rasmussen","sequence":"additional","affiliation":[{"name":"Department of Medical Endocrinology and Metabolism Copenhagen University Hospital Rigshospitalet  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,5,12]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM196705252762101"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2009.01.003"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2014.09.001"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-015-0253-6"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/00365513.2017.1390782"},{"key":"e_1_2_6_7_1","unstructured":"Fabry\u2010Database Index Page.http:\/\/fabry-database.org\/. 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