{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T16:59:30Z","timestamp":1782320370235,"version":"3.54.5"},"reference-count":19,"publisher":"The Endocrine Society","issue":"8","license":[{"start":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T00:00:00Z","timestamp":1752105600000},"content-version":"vor","delay-in-days":27,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014931","name":"Arrowhead Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014931","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Severe hypertriglyceridemia (HTG) is characterized by plasma triglyceride (TG) levels &amp;gt;500\u2005mg\/dL (SI: 5.7\u2005mmol\/L) (reference range, &amp;lt;150\u2005mg\/dL [SI: &amp;lt;1.7\u2005mmol\/L]) and is linked to cardiovascular disease and pancreatitis risk. Treatment typically involves dietary restrictions and lipid-lowering medications. Glycerol kinase deficiency (GKD) is a rare genetic disorder that causes pseudo-HTG.<\/jats:p>\n               <jats:p>In SHASTA-2, a study of patients with severe HTG, most subjects (&amp;gt;90%) treated with plozasiran, an apolipoprotein C-III (APOC3) small interfering RNA (siRNA), achieved TG levels &amp;lt;500\u2005mg\/dL (SI: 5.7\u2005mmol\/L), below the risk threshold for acute pancreatitis. We report herein a case study of a 65-year-old male apparently not responding to plozasiran. The patient was shown to carry a loss-of-function variant in the GK gene resulting in GKD, with high free glycerol (40.24\u2005mg\/dL or 4.37\u2005mmol\/L) (reference range, 0.03-0.13\u2005mmol\/L) that contributed to an overestimation of TG concentration. After correcting for free glycerol, the patient was noted to have had mild HTG, with plozasiran treatment decreasing real TG values by up to 71%.<\/jats:p>\n               <jats:p>This case report suggests that in the absence of response to APOC3 inhibition, measuring free glycerol could be clinically relevant. It also highlights that APOC3 inhibition has no effect on free glycerol concentration.<\/jats:p>","DOI":"10.1210\/jcemcr\/luaf146","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T08:33:22Z","timestamp":1752136402000},"source":"Crossref","is-referenced-by-count":1,"title":["Glycerol Kinase Gene Variant as a Cause of Pseudohypertriglyceridemia and Apparent Poor Response to Plozasiran"],"prefix":"10.1210","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-2356-5396","authenticated-orcid":false,"given":"Miriam","family":"Larouche","sequence":"first","affiliation":[{"name":"Department of Medicine, Universit\u00e9 de Montr\u00e9al and ECOGENE-21 , Chicoutimi, QC G7H 7K9 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christie","family":"Ballantyne","sequence":"additional","affiliation":[{"name":"Internal Medicine, Baylor College of Medicine , Houston, TX 77046 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Universit\u00e9 de Montr\u00e9al and ECOGENE-21 , Chicoutimi, QC G7H 7K9 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2025,7,10]]},"reference":[{"issue":"47","key":"2025071004331676400_luaf146-B1","doi-asserted-by":"crossref","first-page":"4791","DOI":"10.1093\/eurheartj\/ehab551","article-title":"Triglyceride-rich lipoproteins and their remnants: metabolic insights, role in atherosclerotic cardiovascular disease, and emerging therapeutic strategies-a consensus statement from the European atherosclerosis society","volume":"42","author":"Ginsberg","year":"2021","journal-title":"Eur Heart J"},{"issue":"2","key":"2025071004331676400_luaf146-B2","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1097\/MED.0000000000000903","article-title":"An overview of persistent chylomicronemia: much more than meets the eye","volume":"32","author":"Larouche","year":"2025","journal-title":"Curr Opin Endocrinol Diabetes 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