Familial Chylomicronemia Syndrome With a Novel Homozygous <i>LPL</i> Mutation Identified in Three Siblings in Their 50s
Authors: Masako Ueda, Frances M. Burke, Alan T. Remaley, Robert A. Hegele, Daniel J. Rader, Richard L. Dunbar
Journal: Annals of Internal Medicine (2019)

Letters7 April 2020Familial Chylomicronemia Syndrome With a Novel Homozygous LPL Mutation Identified in Three Siblings in Their 50sMasako Ueda, MD, Frances M. Burke, MS, RD, Alan T. Remaley, MD, PhD, Robert A. Hegele, MD, Daniel J. Rader, MD, and Richard L. Dunbar, MD, MSTRMasako Ueda, MDUniversity of Pennsylvania, Philadelphia, Pennsylvania (M.U.), Frances M. Burke, MS, RDUniversity of Pennsylvania Health System, Philadelphia, Pennsylvania (F.M.B.), Alan T. Remaley, MD, PhDNational Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland (A.T.R.), Robert A. Hegele, MDSchulich School of Medicine and Dentistry, Western University, London, Ontario, Canada (R.A.H.), Daniel J. Rader, MDUniversity of Pennsylvania and University of Pennsylvania Health System, Philadelphia, Pennsylvania (D.J.R.), and Richard L. Dunbar, MD, MSTRUniversity of Pennsylvania and Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania (R.L.D.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/L19-0568 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Background: Hypertriglyceridemia (HTG) is a common disorder; it is typically polygenic with a complex genetic architecture and is often multifactorial (1). In contrast, familial chylomicronemia syndrome (FCS) (also called type I hyperlipoproteinemia [Online Mendelian Inheritance in Man identifier: 238600]) with severe HTG is a rare and underdiagnosed monogenic disorder, with an estimated prevalence of 1 case per 1 000 000 persons. Biallelic mutations in the genes encoding lipoprotein lipase (LPL), apolipoprotein (apo)C-II (APOC2), apoA-V (APOA5), lipase maturation factor 1 (LMF1), and glycosylphosphatidylinositol-anchored high-density lipoprotein–binding protein 1 (GPIHBP1) are known causes of FCS, resulting in a deficiency in LPL or its function (2).... References1. Hegele RA, Ginsberg HN, Chapman MJ, et al; European Atherosclerosis Society Consensus Panel. The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management. Lancet Diabetes Endocrinol. 2014;2:655-66. [PMID: 24731657] doi:10.1016/S2213-8587(13)70191-8 CrossrefMedlineGoogle Scholar2. Brahm AJ, Hegele RA. Chylomicronaemia—current diagnosis and future therapies. Nat Rev Endocrinol. 2015;11:352-62. [PMID: 25732519] doi:10.1038/nrendo.2015.26 CrossrefMedlineGoogle Scholar3. de Graaf J, Couture P, Sniderman A. A diagnostic algorithm for the atherogenic apolipoprotein B dyslipoproteinemias. Nat Clin Pract Endocrinol Metab. 2008;4:608-18. [PMID: 18838971] doi:10.1038/ncpendmet0982 CrossrefMedlineGoogle Scholar4. Johansen CT, Dubé JB, Loyzer MN, et al. LipidSeq: a next-generation clinical resequencing panel for monogenic dyslipidemias. J Lipid Res. 2014;55:765-72. [PMID: 24503134] doi:10.1194/jlr.D045963 CrossrefMedlineGoogle Scholar5. Stahel P, Xiao C, Hegele RA, et al. Polygenic risk for hypertriglyceridemia can mimic a major monogenic mutation [Letter]. Ann Intern Med. 2017;167:360-1. [PMID: 28738411]. doi:10.7326/L17-0182 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: University of Pennsylvania, Philadelphia, Pennsylvania (M.U.)University of Pennsylvania Health System, Philadelphia, Pennsylvania (F.M.B.)National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland (A.T.R.)Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada (R.A.H.)University of Pennsylvania and University of Pennsylvania Health System, Philadelphia, Pennsylvania (D.J.R.)University of Pennsylvania and Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania (R.L.D.)Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L19-0568.This article was published at Annals.org on 19 November 2019. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 7 April 2020Volume 172, Issue 7Page: 500-502KeywordsAcute pancreatitisAdolescentsCholesterolDietDisclosureDrug administrationFatsLipasesPancreatitisTwins ePublished: 19 November 2019 Issue Published: 7 April 2020 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...