{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T02:45:31Z","timestamp":1782960331342,"version":"3.54.5"},"reference-count":11,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013220","name":"Ultragenyx Pharmaceutical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013220","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>Homozygous familial hypercholesterolemia (HoFH) is a rare and life-threatening genetic disorder characterized by extremely elevated low-density lipoprotein cholesterol (LDL-C) levels from birth, leading to accelerated atherosclerotic cardiovascular disease and premature mortality. Conventional lipid-lowering therapies often provide insufficient LDL-C reduction, particularly in patients with minimal or absent LDL receptor (LDLR) function. Evinacumab, an angiopoietin-like protein 3 (ANGPTL3) inhibitor, lowers LDL-C independently of LDLR activity and represents a major therapeutic advance. Here we report two Mexican pediatric patients with HoFH who demonstrated profound LDL-C reductions following initiation of Evinacumab (59% and 68% within the first month of treatment), exceeding reductions observed in pivotal clinical trials. Both patients maintained sustained LDL-C reductions during long-term follow-up (up to 22 months). Importantly, temporary treatment interruption in both cases due to administrative and supply related difficulties limited access to Evinacumab was associated with marked rebound hypercholesterolemia. Reinitiation of therapy led to rapid and substantial lipid reduction, demonstrating a clear dechallenge\u2013rechallenge effect and confirming the relevance of a continuous pharmacologic treatment with ANGPTL3 inhibition. Serial vascular imaging in one patient revealed partial regression of subclavian and carotid artery stenosis, as well as reduced aortic wall thickening following sustained LDL-C reduction; adding evidence to the recently described vascular improvement associated with Evinacumab therapy in pediatric HoFH. Both patients also experienced clinically meaningful improvements in quality of life, and treatment was well tolerated without serious adverse events.<\/jats:p>","DOI":"10.3389\/fgene.2026.1841116","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T02:09:01Z","timestamp":1782958141000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Homozygous familial hypercholesterolemia, experience with Evinacumab treatment in two Mexican pediatric patients: case report"],"prefix":"10.3389","volume":"17","author":[{"given":"Ram\u00f3n","family":"Madriz Prado","sequence":"first","affiliation":[{"name":"Servicio de Endocrinolog\u00eda Pedi\u00e1trica, Unidad de Especialidades M\u00e9dicas, Secretar\u00eda de La Defensa Nacional","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yazm\u00edn Guadalupe","family":"R\u00edos Sol\u00eds","sequence":"additional","affiliation":[{"name":"Servicio de Endocrinolog\u00eda Pedi\u00e1trica, Unidad de Especialidades M\u00e9dicas, Secretar\u00eda de La Defensa Nacional","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana Estefan\u00eda","family":"Guerrero D\u00e1vila","sequence":"additional","affiliation":[{"name":"Servicio de Endocrinolog\u00eda Pedi\u00e1trica, Unidad de Especialidades M\u00e9dicas, Secretar\u00eda de La Defensa Nacional","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc\u00eda","family":"Molina Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Servicio de Endocrinolog\u00eda Pedi\u00e1trica, Unidad de Especialidades M\u00e9dicas, Secretar\u00eda de La Defensa Nacional","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar Spencer","family":"Aguilar Reyes","sequence":"additional","affiliation":[{"name":"Servicio de Endocrinolog\u00eda Pedi\u00e1trica, Unidad de Especialidades M\u00e9dicas, Secretar\u00eda de La Defensa Nacional","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilse","family":"Ord\u00f3\u00f1ez","sequence":"additional","affiliation":[{"name":"Servicio de Endocrinolog\u00eda Pedi\u00e1trica, Unidad de Especialidades M\u00e9dicas, Secretar\u00eda de La Defensa Nacional","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leticia","family":"Ramos","sequence":"additional","affiliation":[{"name":"Servicio de Endocrinolog\u00eda Pedi\u00e1trica, Unidad de Especialidades M\u00e9dicas, Secretar\u00eda de La Defensa Nacional","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisol","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"4024","DOI":"10.57187\/s.4024","article-title":"Evinacumab for the treatment of homozygous familial hypercholesterolaemia: first patient case report in Switzerland","volume":"155","author":"Corpataux","year":"2025","journal-title":"Swiss Med. Wkly."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2277","DOI":"10.1093\/eurheartj\/ehad197","article-title":"2023 update on european atherosclerosis society consensus statement on homozygous familial hypercholesterolaemia: new treatments and clinical guidance","volume":"44","author":"Cuchel","year":"2023","journal-title":"Eur. Heart J."},{"key":"B3","doi-asserted-by":"publisher","first-page":"17093","DOI":"10.1038\/nrdp.2017.93","article-title":"Familial hypercholesterolaemia","volume":"3","author":"Defesche","year":"2017","journal-title":"Nat. Rev. Dis. Prim."},{"key":"B4","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1016\/j.jacl.2025.02.012","article-title":"Safety and effectiveness of evinacumab in an infant with homozygous familial hypercholesterolemia: a new renaissance for the very young?","volume":"19","author":"Fornari","year":"2025","journal-title":"J. Clin. Lipidol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"2465","DOI":"10.1007\/s12325-025-03160-4","article-title":"Evinacumab for homozygous familial hypercholesterolemia: the Italian cohort of the ELIPSE HoFH study","volume":"42","author":"Iannuzzo","year":"2025","journal-title":"Adv. Ther."},{"key":"B6","doi-asserted-by":"publisher","first-page":"323","DOI":"10.5551\/jat.65925","article-title":"Evinacumab improved the homozygous familial hypercholesterolemia lipid metabolism: a case report","volume":"32","author":"Matsuda","year":"2025","journal-title":"J. Atheroscler. Thrombosis"},{"key":"B7","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1056\/NEJMoa2004215","article-title":"Evinacumab for homozygous familial hypercholesterolemia","volume":"383","author":"Raal","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.atherosclerosis.2021.04.014","article-title":"Marked plaque regression in homozygous familial hypercholesterolemia","volume":"327","author":"Reeskamp","year":"2021","journal-title":"Atherosclerosis"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1389","DOI":"10.3390\/ph15111389","article-title":"Long-term efficacy and safety of evinacumab in patients with homozygous familial hypercholesterolemia: real-world clinical experience","volume":"15","author":"Stefanutti","year":"2022","journal-title":"Pharmaceuticals"},{"key":"B10","volume-title":"Informaci\u00f3n Para Prescribir Reducida Evkeeza\u00ae (Evinacumab)","year":"2023"},{"key":"B11","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1161\/CIRCULATIONAHA.123.065529","article-title":"Evinacumab for pediatric patients with homozygous familial hypercholesterolemia","volume":"149","author":"Wiegman","year":"2024","journal-title":"Circulation"}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2026.1841116\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T02:09:03Z","timestamp":1782958143000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2026.1841116\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,2]]},"references-count":11,"alternative-id":["10.3389\/fgene.2026.1841116"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2026.1841116","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,2]]},"article-number":"1841116"}}