{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T09:40:01Z","timestamp":1752140401869,"version":"3.41.2"},"reference-count":12,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T00:00:00Z","timestamp":1751932800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T00:00:00Z","timestamp":1751932800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Hematopathol"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Familial erythrocytosis type 3 (ECYT3) is a rare condition caused by loss of function germline mutations in the prolyl hydroxylase domain-2 (PHD2), a regulator in the hypoxia-sensing pathway. Although mutations in PHD2 have been previously described, this particular variant lacks clinical characterization and presents with an aggressive course. We report the case of a patient with vasomotor symptoms and elevations in hematocrit (HCT) and hemoglobin (Hgb) despite frequent therapeutic phlebotomy. He had a family history of erythrocytosis spanning four generations. Germline genetic testing revealed a rare pathogenic variant of PHD2, confirming a diagnosis of ECYT3. Therapeutic phlebotomy yielded only transient Hgb and HCT reductions and only partial symptomatic control. This case highlights the diagnostic challenges and limitations of current treatments for hereditary erythrocytosis and underscores the need for symptom-centered management strategies. Furthermore, we highlight a gap in the literature around the pathophysiology and management of ECYT3.<\/jats:p>","DOI":"10.1007\/s12308-025-00645-7","type":"journal-article","created":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T04:36:19Z","timestamp":1751949379000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["EGLN1-positive familial erythrocytosis: a rare variant with an unusually aggressive clinical course"],"prefix":"10.1007","volume":"18","author":[{"given":"Laura","family":"Maule","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brielle","family":"Coe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rishi","family":"Sawhney","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,7,8]]},"reference":[{"issue":"16","key":"645_CR1","doi-asserted-by":"publisher","first-page":"2441","DOI":"10.1182\/blood.2021011043","volume":"139","author":"GL Semenza","year":"2022","unstructured":"Semenza GL (2022) Breakthrough science: hypoxia-inducible factors, oxygen sensing, and disorders of hematopoiesis. Blood 139(16):2441\u20132449. https:\/\/doi.org\/10.1182\/blood.2021011043","journal-title":"Blood"},{"key":"645_CR2","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1002\/ajh.25150","volume":"93","author":"JL Oliveira","year":"2018","unstructured":"Oliveira JL, Coon LM, Frederick LA et al (2018) Genotype\u2013phenotype correlation of hereditary erythrocytosis mutations, a single center experience. Am J Hematol 93:1029\u20131041. https:\/\/doi.org\/10.1002\/ajh.25150","journal-title":"Am J Hematol"},{"issue":"6","key":"645_CR3","doi-asserted-by":"publisher","first-page":"2148","DOI":"10.1182\/blood.v89.6.2148","volume":"89","author":"Adelina Sergeyeva","year":"1997","unstructured":"Sergeyeva Adelina et al (1997) Congenital polycythemia in Chuvashia. Blood 89(6):2148\u20132154. https:\/\/doi.org\/10.1182\/blood.v89.6.2148","journal-title":"Blood"},{"issue":"6","key":"645_CR4","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/j.blre.2008.04.003","volume":"22","author":"FS Lee","year":"2008","unstructured":"Lee FS (2008) Genetic causes of erythrocytosis and the oxygen-sensing pathway. Blood Rev 22(6):321\u2013332. https:\/\/doi.org\/10.1016\/j.blre.2008.04.003","journal-title":"Blood Rev"},{"issue":"4","key":"645_CR5","doi-asserted-by":"publisher","first-page":"220","DOI":"10.2478\/ahp-2020-0038","volume":"51","author":"M Pepek","year":"2020","unstructured":"Pepek M et al (2020) First familial cases of type 2 congenital erythrocytosis (ECYT2) with a Chuvash pathogenic variant in VHL gene in Poland: example of the clinical utility of next-generation sequencing in diagnostics of orphan diseases. Acta Haematologica Polonica 51(4):220\u2013225. https:\/\/doi.org\/10.2478\/ahp-2020-0038","journal-title":"Acta Haematologica Polonica"},{"key":"645_CR6","unstructured":"Entry - #609820 - Erythrocytosis, Familial, 3; ECYT3 - OMIM. omim.org\/entry\/609820. Accessed 20 Apr 2025"},{"issue":"6319","key":"645_CR7","doi-asserted-by":"publisher","first-page":"aaf6814","DOI":"10.1126\/science.aaf6814","volume":"354","author":"FE Dewey","year":"2016","unstructured":"Dewey FE, Murray MF, Overton JD et al (2016) Distribution and clinical impact of functional variants in 50,726 whole-exome sequences from the DiscovEHR study. Science 354(6319):aaf6814. https:\/\/doi.org\/10.1126\/science.aaf6814","journal-title":"Science"},{"issue":"25","key":"645_CR8","doi-asserted-by":"publisher","first-page":"2685","DOI":"10.1056\/nejmoa0806277","volume":"359","author":"Charline Ladroue","year":"2008","unstructured":"Ladroue Charline et al (2008) PHD2 mutation and congenital erythrocytosis with paraganglioma. New Engl J Med 359(25):2685\u20132692. https:\/\/doi.org\/10.1056\/nejmoa0806277","journal-title":"New Engl J Med"},{"key":"645_CR9","doi-asserted-by":"publisher","first-page":"4393","DOI":"10.1113\/jp275996","volume":"596","author":"James W Fielding","year":"2018","unstructured":"Fielding James W et al (2018) PHD2 inactivation in type I cells drives hif-2\u03b1-dependent multilineage hyperplasia and the formation of paraganglioma-like carotid bodies. J Physiol 596:4393\u20134412. https:\/\/doi.org\/10.1113\/jp275996","journal-title":"J Physiol"},{"key":"645_CR10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2016\/6373706","volume":"2016","author":"R Wilson","year":"2016","unstructured":"Wilson R et al (2016) Erythrocytosis due to PHD2 mutations: a review of clinical presentation, diagnosis, and Genetics. Case Rep Hematol 2016:1\u20138. https:\/\/doi.org\/10.1155\/2016\/6373706","journal-title":"Case Rep Hematol"},{"key":"645_CR11","unstructured":"Gazenko LO (1992) Pathogenetic features of hereditary erythrocytosis. Hematological Scientific Center. Doctoral Dissertation, Moscow, Russia"},{"issue":"5","key":"645_CR12","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1182\/blood-2018-03-838235","volume":"132","author":"Marion Lenglet","year":"2018","unstructured":"Lenglet Marion et al (2018) Identification of a new VHL exon and complex splicing alterations in familial erythrocytosis or von Hippel-Lindau disease. Blood 132(5):469\u2013483. https:\/\/doi.org\/10.1182\/blood-2018-03-838235","journal-title":"Blood"}],"container-title":["Journal of Hematopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12308-025-00645-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12308-025-00645-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12308-025-00645-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T09:12:17Z","timestamp":1752138737000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12308-025-00645-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,8]]},"references-count":12,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["645"],"URL":"https:\/\/doi.org\/10.1007\/s12308-025-00645-7","relation":{},"ISSN":["1868-9256","1865-5785"],"issn-type":[{"value":"1868-9256","type":"print"},{"value":"1865-5785","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,8]]},"assertion":[{"value":"21 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 June 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 July 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This case report was conducted in accordance with institutional and international guidelines. Ethical approval was not required for this single-case report as no identifiable patient data, images, or institutional details are disclosed.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"The patient provided consent to participate in this case report.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"value":"The patient provided consent for the publication of this manuscript.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"30"}}