{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:48:41Z","timestamp":1791287321179,"version":"4.1.0"},"reference-count":26,"publisher":"The Endocrine Society","issue":"4","license":[{"start":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T00:00:00Z","timestamp":1725580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Patients with rare familial chylomicronemia syndrome (FCS) and relatively common multifactorial chylomicronemia syndrome (MCS) both express severe hypertriglyceridemia, defined as plasma triglyceride concentration \u226510\u2005mmol\/L (\u2265885\u2005mg\/dL). Clinically there can be confusion between the 2 conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To compare clinical and biochemical phenotypes in patients with genotypically characterized FCS and MCS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed targeted sequencing of DNA from 193 patients with severe hypertriglyceridemia, classified them as having either FCS or MCS, and compared clinical and biochemical characteristics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Patients with FCS were significantly younger than patients with MCS (31.4 \u00b1 16.7 vs 51.0 \u00b1 11.3 years; P = .003), with earlier age at symptom onset (15.0 \u00b1 15.8 vs 37.8 \u00b1 8.8 years; P = .00066), lower body mass index (23.3 \u00b1 3.1 vs 30.7 \u00b1 5.0\u2005kg\/m2; P = .000016), and higher prevalence of pancreatitis events (81.8% vs 35.2%; P = .003). Furthermore, patients with FCS had a higher ratio of triglyceride to total cholesterol (ie, 4.18 \u00b1 0.92 vs 1.08 \u00b1 0.51; P &amp;lt; .0001) and lower plasma apolipoprotein B (ie, 0.56 \u00b1 0.15 vs 1.02 \u00b1 0.43\u2005g\/L; P &amp;lt; .0001) than patients with MCS. Patients with MCS with heterozygous pathogenic variants had a relatively more severe clinical presentation than other MCS genetic subgroups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Patients with FCS have notable phenotypic differences from patients with MCS, although there is overlap. While genetic analysis of patients with persistent severe hypertriglyceridemia can definitively diagnose FCS, 8.8% of patients with MCS with sustained refractory hypertriglyceridemia behave functionally as if they have FCS, which should influence their eligibility for novel therapies for severe hypertriglyceridemia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgae613","type":"journal-article","created":{"date-parts":[[2024,9,3]],"date-time":"2024-09-03T23:51:48Z","timestamp":1725407508000},"page":"1158-1165","source":"Crossref","is-referenced-by-count":30,"title":["Comparison of Patients With Familial Chylomicronemia Syndrome and Multifactorial Chylomicronemia Syndrome"],"prefix":"10.1210","volume":"110","author":[{"given":"Catherine M","family":"Spagnuolo","sequence":"first","affiliation":[{"name":"Department of Medicine, Schulich School of Medicine and Dentistry, Western University , London, Ontario, Canada, N6A 5B7"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wang","sequence":"additional","affiliation":[{"name":"Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University , London, Ontario, Canada, N6A 5B7"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam D","family":"McIntyre","sequence":"additional","affiliation":[{"name":"Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University , London, Ontario, Canada, N6A 5B7"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brooke A","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University , London, Ontario, Canada, N6A 5B7"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2861-5325","authenticated-orcid":false,"given":"Robert A","family":"Hegele","sequence":"additional","affiliation":[{"name":"Department of Medicine, Schulich School of Medicine and Dentistry, Western University , London, Ontario, Canada, N6A 5B7"},{"name":"Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University , London, Ontario, Canada, N6A 5B7"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2024,9,6]]},"reference":[{"key":"2025031717041529700_dgae613-B1","doi-asserted-by":"crossref","first-page":"455","DOI":"10.3389\/fendo.2020.00455","article-title":"Genetics of hypertriglyceridemia","volume":"11","author":"Dron","year":"2020","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"9","key":"2025031717041529700_dgae613-B2","doi-asserted-by":"crossref","first-page":"626","DOI":"10.7326\/M19-0203","article-title":"The chylomicronemia syndrome is most often multifactorial: a narrative review of causes and treatment","volume":"170","author":"Chait","year":"2019","journal-title":"Ann Intern Med"},{"issue":"4","key":"2025031717041529700_dgae613-B3","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1111\/joim.13016","article-title":"Familial chylomicronemia syndrome: an under-recognized cause of severe hypertriglyceridaemia","volume":"287","author":"Baass","year":"2020","journal-title":"J Intern Med"},{"issue":"1","key":"2025031717041529700_dgae613-B4","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1186\/s12944-021-01517-6","article-title":"Incidence, predictors and patterns of care of patients with very severe hypertriglyceridemia in Ontario, Canada: a population-based cohort study","volume":"20","author":"Berberich","year":"2021","journal-title":"Lipids Health Dis"},{"issue":"4","key":"2025031717041529700_dgae613-B5","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1080\/17512433.2022.2094768","article-title":"Safety and efficacy of therapies for chylomicronemia","volume":"15","author":"Shamsudeen","year":"2022","journal-title":"Expert Rev Clin Pharmacol"},{"issue":"10","key":"2025031717041529700_dgae613-B6","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1007\/s11883-023-01140-z","article-title":"Updates in drug treatment of severe hypertriglyceridemia","volume":"25","author":"Gouni-Berthold","year":"2023","journal-title":"Curr Atheroscler Rep"},{"issue":"1","key":"2025031717041529700_dgae613-B7","doi-asserted-by":"crossref","first-page":"2","DOI":"10.12997\/jla.2024.13.1.2","article-title":"Advances in dyslipidaemia treatments: focusing on ApoC3 and ANGPTL3 inhibitors","volume":"13","author":"Tomlinson","year":"2024","journal-title":"J Lipid Atheroscler"},{"issue":"5","key":"2025031717041529700_dgae613-B8","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1056\/NEJMc2306575","article-title":"Volanesorsen to prevent acute pancreatitis in hypertriglyceridemia","volume":"390","author":"Alexander","year":"2024","journal-title":"N Engl J Med"},{"issue":"19","key":"2025031717041529700_dgae613-B9","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1056\/NEJMoa2400201","article-title":"Olezarsen, acute pancreatitis, and familial chylomicronemia syndrome","volume":"390","author":"Stroes","year":"2024","journal-title":"N Engl J Med"},{"issue":"5","key":"2025031717041529700_dgae613-B10","doi-asserted-by":"crossref","first-page":"621","DOI":"10.3390\/metabo13050621","article-title":"Severe hypertriglyceridaemia and chylomicronaemia syndrome-causes, clinical presentation, and therapeutic options","volume":"13","author":"Bashir","year":"2023","journal-title":"Metabolites"},{"issue":"1","key":"2025031717041529700_dgae613-B11","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.jacl.2018.10.006","article-title":"Severe hypertriglyceridemia is primarily polygenic","volume":"13","author":"Dron","year":"2019","journal-title":"J Clin Lipidol"},{"issue":"8","key":"2025031717041529700_dgae613-B12","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/S2213-8587(13)70191-8","article-title":"The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management","volume":"2","author":"Hegele","year":"2014","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"4","key":"2025031717041529700_dgae613-B13","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1194\/jlr.D045963","article-title":"LipidSeq: a next-generation clinical resequencing panel for monogenic dyslipidemias","volume":"55","author":"Johansen","year":"2014","journal-title":"J Lipid Res"},{"issue":"1","key":"2025031717041529700_dgae613-B14","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s12920-020-0669-2","article-title":"Six years\u2019 experience with LipidSeq: clinical and research learnings from a hybrid, targeted sequencing panel for dyslipidemias","volume":"13","author":"Dron","year":"2020","journal-title":"BMC Med Genomics"},{"key":"2025031717041529700_dgae613-B15","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.atherosclerosis.2018.06.814","article-title":"Identification and diagnosis of patients with familial chylomicronaemia syndrome (FCS): expert panel recommendations and proposal of an \u201cFCS score\u201d","volume":"275","author":"Moulin","year":"2018","journal-title":"Atherosclerosis"},{"issue":"11","key":"2025031717041529700_dgae613-B16","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1038\/ng.2797","article-title":"Discovery and refinement of loci associated with lipid levels","volume":"45","author":"Willer","year":"2013","journal-title":"Nat Genet"},{"issue":"16","key":"2025031717041529700_dgae613-B17","doi-asserted-by":"crossref","first-page":"e164","DOI":"10.1093\/nar\/gkq603","article-title":"ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data","volume":"38","author":"Wang","year":"2010","journal-title":"Nucleic Acids Res"},{"issue":"5","key":"2025031717041529700_dgae613-B18","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American college of medical genetics and genomics and the association for molecular pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med"},{"issue":"4","key":"2025031717041529700_dgae613-B19","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1016\/j.jacl.2018.03.093","article-title":"Clinical and biochemical features of different molecular etiologies of familial chylomicronemia","volume":"12","author":"Hegele","year":"2018","journal-title":"J Clin Lipidol"},{"key":"2025031717041529700_dgae613-B20","doi-asserted-by":"publisher","DOI":"10.5683\/SP3\/MZB2MZ"},{"issue":"8","key":"2025031717041529700_dgae613-B21","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1161\/ATVBAHA.120.314168","article-title":"Loss-of-function CREB3L3 variants in patients with severe hypertriglyceridemia","volume":"40","author":"Dron","year":"2020","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2025031717041529700_dgae613-B22","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.atherosclerosis.2018.12.019","article-title":"Chylomicronemia: differences between familial chylomicronemia syndrome and multifactorial chylomicronemia","volume":"283","author":"Paquette","year":"2019","journal-title":"Atherosclerosis"},{"issue":"12","key":"2025031717041529700_dgae613-B23","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1210\/js.2019-00214","article-title":"Differentiating familial chylomicronemia syndrome from multifactorial severe hypertriglyceridemia by clinical profiles","volume":"3","author":"O'Dea","year":"2019","journal-title":"J Endocr Soc"},{"issue":"3","key":"2025031717041529700_dgae613-B24","doi-asserted-by":"crossref","first-page":"e1332","DOI":"10.1210\/clinem\/dgaa838","article-title":"10-year comparative follow-up of familial versus multifactorial chylomicronemia syndromes","volume":"106","author":"elhassen","year":"2021","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"2025031717041529700_dgae613-B25","doi-asserted-by":"crossref","first-page":"bvaa056","DOI":"10.1210\/jendso\/bvaa056","article-title":"Dissection of clinical and gene expression signatures of familial versus multifactorial chylomicronemia","volume":"4","author":"Tremblay","year":"2020","journal-title":"J Endocr Soc"},{"issue":"4","key":"2025031717041529700_dgae613-B26","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1210\/endrev\/bnab037","article-title":"A modern approach to dyslipidemia","volume":"43","author":"Berberich","year":"2022","journal-title":"Endocr Rev"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgae613\/59314214\/dgae613.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/110\/4\/1158\/59314214\/dgae613.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/110\/4\/1158\/59314214\/dgae613.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T13:04:31Z","timestamp":1742216671000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/110\/4\/1158\/7750066"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,6]]},"references-count":26,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,9,6]]},"published-print":{"date-parts":[[2025,3,17]]}},"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgae613","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,4]]},"published":{"date-parts":[[2024,9,6]]}}}