{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:49:09Z","timestamp":1790812149099,"version":"4.1.0"},"reference-count":148,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,4,30]],"date-time":"2023-04-30T00:00:00Z","timestamp":1682812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>We have reviewed the genetic basis of chylomicronaemia, the difference between monogenic and polygenic hypertriglyceridaemia, its effects on pancreatic, cardiovascular, and microvascular complications, and current and potential future pharmacotherapies. Severe hypertriglyceridaemia (TG &gt; 10 mmol\/L or 1000 mg\/dL) is rare with a prevalence of &lt;1%. It has a complex genetic basis. In some individuals, the inheritance of a single rare variant with a large effect size leads to severe hypertriglyceridaemia and fasting chylomicronaemia of monogenic origin, termed as familial chylomicronaemia syndrome (FCS). Alternatively, the accumulation of multiple low-effect variants causes polygenic hypertriglyceridaemia, which increases the tendency to develop fasting chylomicronaemia in presence of acquired factors, termed as multifactorial chylomicronaemia syndrome (MCS). FCS is an autosomal recessive disease characterized by a pathogenic variant of the lipoprotein lipase (LPL) gene or one of its regulators. The risk of pancreatic complications and associated morbidity and mortality are higher in FCS than in MCS. FCS has a more favourable cardiometabolic profile and a low prevalence of atherosclerotic cardiovascular disease (ASCVD) compared to MCS. The cornerstone of the management of severe hypertriglyceridaemia is a very-low-fat diet. FCS does not respond to traditional lipid-lowering therapies. Several novel pharmacotherapeutic agents are in various phases of development. Data on the correlation between genotype and phenotype in FCS are scarce. Further research to investigate the impact of individual gene variants on the natural history of the disease, and its link with ASCVD, microvascular disease, and acute or recurrent pancreatitis, is warranted. Volanesorsen reduces triglyceride concentration and frequency of pancreatitis effectively in patients with FCS and MCS. Several other therapeutic agents are in development. Understanding the natural history of FCS and MCS is necessary to rationalise healthcare resources and decide when to deploy these high-cost low-volume therapeutic agents.<\/jats:p>","DOI":"10.3390\/metabo13050621","type":"journal-article","created":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T12:14:08Z","timestamp":1682943248000},"page":"621","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Severe Hypertriglyceridaemia and Chylomicronaemia Syndrome\u2014Causes, Clinical Presentation, and Therapeutic Options"],"prefix":"10.3390","volume":"13","author":[{"given":"Bilal","family":"Bashir","sequence":"first","affiliation":[{"name":"Faculty of Biology Medicine and Health, University of Manchester, Manchester M13 9PL, UK"},{"name":"Department of Endocrinology, Diabetes & Metabolism, Manchester University NHS Foundation Trust, Manchester M13 9WL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan H.","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Downie","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Salisbury NHS Foundation Trust, Salisbury SP2 8BJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Hamilton","sequence":"additional","affiliation":[{"name":"Centre for Medical Education, Queen\u2019s University Belfast, Belfast BT7 1NN, UK"},{"name":"Department of Clinical Biochemistry, Belfast Health and Social Care Trust, Belfast BT13 1FD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon","family":"Ferns","sequence":"additional","affiliation":[{"name":"Brighton and Sussex Medical School, Brighton BN1 9PH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dev","family":"Datta","sequence":"additional","affiliation":[{"name":"Lipid Unit, University Hospital Llandough, Cardiff CF64 2XX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaimini","family":"Cegla","sequence":"additional","affiliation":[{"name":"Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London SW7 2BX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2756-372X","authenticated-orcid":false,"given":"Anthony S.","family":"Wierzbicki","sequence":"additional","affiliation":[{"name":"Department of Metabolic Medicine and Chemical Pathology, Guy\u2019s and St. Thomas\u2019 Hospitals, London SE1 7EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Dawson","sequence":"additional","affiliation":[{"name":"Department of Metabolic Medicine, Queen Elizabeth Hospital NHS Foundation 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