{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T15:23:40Z","timestamp":1787757820249,"version":"build-2784847793"},"reference-count":18,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>\n                    A\n                    <jats:sc>BSTRACT<\/jats:sc>\n                  <\/jats:title>\n                  <jats:p>\n                    Fabry disease (FD) is a rare X-linked lysosomal storage disorder characterized by \u03b1-galactosidase A deficiency, marked phenotypic heterogeneity, and frequent diagnostic delay. We report a multigenerational family with Fabry disease caused by a\n                    <jats:italic toggle=\"yes\">de novo<\/jats:italic>\n                    GLA (\u03b1-galactosidase A gene) mutation in a female patient, affecting two adult sons and an infant granddaughter. The index patient, a 25-year-old male, experienced neuropathic pain, recurrent unexplained fever, gastrointestinal symptoms, anhidrosis, and cerebrovascular events for more than a decade prior to diagnosis. Cardiac hypertrophy, cornea verticillata, and ischemic cerebral lesions were detected. His mother showed neurological and cardiac involvement and was confirmed to carry a\n                    <jats:italic toggle=\"yes\">de novo<\/jats:italic>\n                    GLA mutation. The younger brother presented a milder phenotype without cardiac or ocular involvement. Early cascade genetic screening enabled diagnosis of an affected infant at 6 months of age. Enzyme replacement therapy (ERT) was initiated in all adult patients, leading to symptomatic improvement, although cerebrovascular events persisted in the index case. This case series highlights the pronounced intrafamilial phenotypic variability of Fabry disease and underscores the need to consider FD even in the absence of a positive family history. Early genetic screening, including prenatal and early postnatal testing, is critical to reduce diagnostic delay and optimize long-term clinical outcomes.\n                  <\/jats:p>","DOI":"10.4103\/jfmpc.jfmpc_2240_25","type":"journal-article","created":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T14:01:03Z","timestamp":1779544863000},"page":"1813-1818","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["A multigenerational fabry disease case caused by a de novo GLA mutation: Diagnostic delay, phenotypic variability, and the impact of early detection"],"prefix":"10.4103","volume":"15","author":[{"given":"Senay","family":"Topsakal","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism, Pamukkale University, Faculty of Medicine, Denizli, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I\u015f\u0131k","family":"Tekin","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Pamukkale University, Faculty of Medicine, Denizli, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selma","family":"Tekin","sequence":"additional","affiliation":[{"name":"Department of Neurology, Pamukkale University, Faculty of Medicine, Denizli, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00fcseyin","family":"Kaya","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Pamukkale University, Faculty of Medicine, Denizli, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vefa","family":"\u00c7akmak","sequence":"additional","affiliation":[{"name":"Department of Radiology, Pamukkale University, Faculty of Medicine, Denizli, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00fcseyin","family":"Onay","sequence":"additional","affiliation":[{"name":"Department of Genetics, Ege University, Faculty of Medicine, Izmir, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,5,23]]},"reference":[{"key":"R1-20260603","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/1750-1172-5-30","article-title":"Fabry disease","volume":"5","author":"Germain","year":"2010","journal-title":"Orphanet J Rare Dis"},{"key":"R2-20260603","doi-asserted-by":"crossref","first-page":"96","DOI":"10.2174\/1566523218666180404161315","article-title":"Genetics and gene therapy of anderson-fabry disease","volume":"18","author":"Simonetta","year":"2018","journal-title":"Curr Gene Ther"},{"key":"R3-20260603","doi-asserted-by":"crossref","first-page":"70","DOI":"10.2174\/1389202918666170915155033","article-title":"Identification of a missense mutation in the ?-galactosidase A gene in a Chinese family with fabry disease","volume":"19","author":"Wu","year":"2017","journal-title":"Curr Genom"},{"key":"R4-20260603","doi-asserted-by":"crossref","first-page":"4926","DOI":"10.21037\/apm-19-635","article-title":"A late-onset male Fabry disease patient with somatic mosaicism of a classical GLA mutation: A case report","volume":"10","author":"Bae","year":"2021","journal-title":"Ann Palli Med"},{"key":"R5-20260603","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1186\/s13104-015-1696-5","article-title":"Late diagnosis of Fabry disease caused by a de novo mutation in a patient with end stage renal disease","volume":"24","author":"Pisani","year":"2015","journal-title":"BMC Res Notes"},{"key":"R6-20260603","doi-asserted-by":"crossref","first-page":"1368953","DOI":"10.3389\/fgene.2024.1368953","article-title":"Corrigendum: Case report: De novo mutation of a-galactosidase A in a female patient with end-stage renal disease: Report of a case of late diagnosis of Anderson-Fabry disease","volume":"15","author":"Simonetta","year":"2024","journal-title":"Front Genet"},{"key":"R7-20260603","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1159\/000496620","article-title":"Fabry disease prevalence in renal replacement therapy in Turkey","volume":"142","author":"Yal\u0131n","year":"2019","journal-title":"Nephron"},{"key":"R8-20260603","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/1756-0500-7-11","article-title":"De novo mutation in a male patient with Fabry disease: A case report","volume":"7","author":"Iemolo","year":"2014","journal-title":"BMC Res Notes"},{"key":"R9-20260603","doi-asserted-by":"crossref","first-page":"3161","DOI":"10.1007\/s11255-024-04042-4","article-title":"Fabry disease: A rare disorder calling for personalized medicine","volume":"56","author":"Lerario","year":"2024","journal-title":"Intern Urol Nephrol"},{"key":"R10-20260603","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.kint.2016.10.004","article-title":"Conference participants screening, diagnosis, and management of patients with Fabry disease: Conclusions from a \u201cKidney Disease: Improving Global Outcomes\u201d (KDIGO) Controversies Conference","volume":"91","author":"Schiffmann","year":"2017","journal-title":"Kidney Intern"},{"key":"R11-20260603","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1007\/s00381-019-04319-5","article-title":"Malformation in defined genetic syndromes in children: Are there common pathways?","volume":"35","author":"Saletti","year":"2019","journal-title":"Child's Nerv Syst"},{"key":"R12-20260603","doi-asserted-by":"crossref","first-page":"5","DOI":"10.47162\/RJME.62.1.01","article-title":"Fabry disease-current data and therapeutic approaches","volume":"62","author":"Dinu","year":"2021","journal-title":"Roman J Morphol Embryol"},{"key":"R13-20260603","doi-asserted-by":"crossref","first-page":"620","DOI":"10.3889\/oamjms.2022.9681","article-title":"Neurological manifestations of fabry disease: Literature review","volume":"10","author":"Grigolashvili","year":"2022","journal-title":"Open Access Maced J Med Sci"},{"key":"R14-20260603","first-page":"52","article-title":"A case of fabry disease presenting with young stroke and fever","volume":"28","author":"Wu","year":"2019","journal-title":"Acta Neurol Taiwan"},{"key":"R15-20260603","first-page":"549","article-title":"Fabry disease: An overlooked diagnosis in adult cardiac patients","volume":"45","author":"Kay\u0131k\u00e7\u0131o\u011flu","year":"2017","journal-title":"Turk Kardiyol Dern Arsivi"},{"key":"R16-20260603","doi-asserted-by":"crossref","first-page":"139","DOI":"10.3390\/diagnostics15020139","article-title":"Anderson-fabry disease: An overview of current diagnosis, arrhythmic risk stratification, and therapeutic strategies","volume":"15","author":"Tognola","year":"2025","journal-title":"Diagnostics (Basel)"},{"key":"R17-20260603","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/s13023-025-03600-y","article-title":"Impact of enzyme replacement therapy and migalastat on disease progression in females with fabry disease","volume":"20","author":"Lenders","year":"2025","journal-title":"Orphanet J Rare Dis"},{"key":"R18-20260603","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1159\/000546085","article-title":"Recent Advances in understanding the pathophysiology of Fabry disease","volume":"149","author":"Warnock","year":"2025","journal-title":"Nephron"}],"container-title":["Journal of Family Medicine and Primary 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