{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T05:06:02Z","timestamp":1780031162265,"version":"3.53.1"},"reference-count":16,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Fabry disease is a rare X-linked lysosomal storage disorder caused by deficiency of \u03b1-galactosidase A, leading to progressive accumulation of globotriaosylceramide and Lyso-Gb3 across multiple organ systems. Timely initiation of enzyme replacement therapy (ERT) is critical to prevent irreversible organ damage; however, access to disease-specific treatment remains limited in many regions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We describe a prospective observational case series representing the first national experience with ERT in North Macedonia in two male patients with advanced Fabry disease following kidney transplantation. Clinical, biochemical, cardiac, neurological, and patient-reported outcomes were prospectively evaluated after initiation of agalsidase beta (1 mg\/kg) and agalsidase alfa (0.2 mg\/kg), respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Both patients demonstrated substantial and sustained reductions in Lyso-Gb3 levels, confirming a robust biochemical response. Renal graft function remained stable without proteinuria, and no progression of cardiac involvement was observed. Clinical response varied between patients: the first patient experienced marked and sustained improvement in neuropathic pain and quality of life, whereas the second patient demonstrated persistent fluctuating neurological manifestations despite significant biochemical response. Persistent neurological impairment in the second patient was associated with combined central and peripheral nervous system involvement, including Fabry-related ischemic encephalopathy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In this two-patient case series, ERT was well-tolerated and associated with substantial reduction of biochemical disease burden and stabilization of renal graft and cardiac function. However, persistent neurological impairment despite marked Lyso-Gb3 reduction suggests limited reversibility of advanced central nervous system involvement, highlighting the importance of early diagnosis, family screening, and timely initiation of disease-specific therapy in Fabry disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1857063","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T04:54:58Z","timestamp":1780030498000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["From diagnosis to disease-specific treatment: first experience with enzyme replacement therapy for Fabry disease in North Macedonia\u2014a case series"],"prefix":"10.3389","volume":"13","author":[{"given":"Vlatko","family":"Karanfilovski","sequence":"first","affiliation":[{"name":"University Clinic for Nephrology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje","place":["Skopje, North Macedonia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor G.","family":"Nikolov","sequence":"additional","affiliation":[{"name":"University Clinic for Nephrology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje","place":["Skopje, North Macedonia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavlina","family":"Dzekova Vidimliski","sequence":"additional","affiliation":[{"name":"University Clinic for Nephrology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje","place":["Skopje, North Macedonia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana Krstevska","family":"Balkanov","sequence":"additional","affiliation":[{"name":"University Clinic for Hematology, Bone Marrow Transplantation Unit, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje","place":["Skopje, North Macedonia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galina","family":"Severova","sequence":"additional","affiliation":[{"name":"University Clinic for Nephrology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje","place":["Skopje, North Macedonia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Stojanoska","sequence":"additional","affiliation":[{"name":"University Clinic for Nephrology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje","place":["Skopje, North Macedonia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikola","family":"Gjorgjievski","sequence":"additional","affiliation":[{"name":"University Clinic for Nephrology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje","place":["Skopje, North Macedonia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1415906","DOI":"10.3389\/fgene.2024.1415906","article-title":"Case report: First diagnosis of Fabry disease in North Macedonia in a patient presenting with kidney failure on hemodialysis.","volume":"15","author":"Gjorgjievski","year":"2024","journal-title":"Front Genet."},{"key":"B2","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1159\/000547144","article-title":"Fabry disease nephropathy: compendium of \u201cin vitro\u201d and \u201cin vivo\u201d renal effects of globotriaosylsphingosine.","volume":"50","author":"Jaurretche","year":"2025","journal-title":"Kidney Blood Press Res."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1662867","DOI":"10.3389\/fmed.2025.1662867","article-title":"Therapeutic landscape of Fabry disease: advances and challenges from classical strategies to emerging therapies.","volume":"12","author":"Zhang","year":"2025","journal-title":"Front Med."},{"key":"B4","volume-title":"Variants Reported for Fabry Disease.","year":"2026"},{"key":"B5","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1097\/GIM.0b013e3181f13b75","article-title":"Effects of enzyme replacement therapy in Fabry disease\u2014A comprehensive review of the medical literature.","volume":"12","author":"Lidove","year":"2010","journal-title":"Genet Med."},{"key":"B6","doi-asserted-by":"publisher","first-page":"5131","DOI":"10.3390\/jcm14145131","article-title":"Clinical efficacy and real-world effectiveness of Fabry disease treatments: a systematic literature review.","volume":"14","author":"Jovanovic","year":"2025","journal-title":"J Clin Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/s13023-015-0253-6","article-title":"Recommendations for initiation and cessation of enzyme replacement therapy in patients with Fabry disease: the European Fabry Working Group consensus document.","volume":"10","author":"Biegstraaten","year":"2015","journal-title":"Orphanet J Rare Dis."},{"key":"B8","first-page":"5","article-title":"Evidence-based guideline for diagnosis, treatment and follow-up of patients with Fabry disease.","volume":"208","year":"2025","journal-title":"Off Gazette Republic North Macedonia."},{"key":"B9","doi-asserted-by":"publisher","first-page":"2989","DOI":"10.3390\/biomedicines13122989","article-title":"Long-term enzyme replacement therapy and renal outcomes in Fabry disease: a systematic review and meta-analysis.","volume":"13","author":"Chen","year":"2025","journal-title":"Biomedicines."},{"key":"B10","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1007\/s40620-024-02170-9","article-title":"Epidemiology and early predictors of Fabry nephropathy: evaluation of long-term outcomes from a national Fabry 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disease.","volume":"28","author":"Schiffmann","year":"2003","journal-title":"Muscle Nerve."},{"key":"B14","doi-asserted-by":"publisher","first-page":"26330040251405830","DOI":"10.1177\/26330040251405830","article-title":"Lysosomal storage diseases in North America: a comprehensive review of enzyme therapies and unmet needs.","volume":"6","author":"Bennett","year":"2025","journal-title":"Ther Adv Rare Dis."},{"key":"B15","doi-asserted-by":"publisher","first-page":"sfaf318","DOI":"10.1093\/ckj\/sfaf318","article-title":"Clinical outcomes in Fabry patients switching to agalsidase beta for renal ineffectiveness of the primary Fabry therapy: a single-centre analysis.","volume":"18","author":"Riccio","year":"2025","journal-title":"Clin Kidney J."},{"key":"B16","doi-asserted-by":"publisher","first-page":"2179","DOI":"10.2165\/11318300-000000000-00000","article-title":"Enzyme replacement therapy for Fabry disease: a systematic review of available evidence.","volume":"69","author":"Schaefer","year":"2009","journal-title":"Drugs."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1857063\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T04:55:03Z","timestamp":1780030503000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1857063\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,29]]},"references-count":16,"alternative-id":["10.3389\/fmed.2026.1857063"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1857063","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,29]]},"article-number":"1857063"}}