Highlights
- •Occasional HTG since childhood aggravated during pregnancy and led to pancreatitis.
- •Strict dietary fat restriction during pregnancy prevented acute pancreatitis.
- •Sequencing analysis revealed a novel homozygous nonsense variant in LMF1.
- •The plasma activities of lipoprotein lipase and hepatic lipase were markedly reduced.
- •Occasional childhood-onset HTG should be suspected for monogenic chylomicronemia.
Abstract
Hypertriglyceridemia (HTG)-induced pancreatitis during pregnancy could lead to maternal
and fetal death. However, its genetic bases are not fully understood, and its treatment
strategies are yet to be established.
Here we report a case with a novel homozygous nonsense variant of LMF1 in pregnancy-associated HTG with acute pancreatitis.
Our patient had childhood-onset severe HTG that had been well-controlled by dietary
management in the non-pregnant period with plasma triglyceride (TG) levels at around
200 mg/dL. Milky plasma was noted at the first-trimester pregnancy checkup, followed
by a severe increase in plasma TG (10,500 mg/dL) that resulted in pancreatitis in
the last trimester. The implementation of strict dietary fat restriction (less than
4 grams per day) reduced plasma TG levels and led to successful delivery. Exome sequencing
revealed a novel homozygous nonsense variant in LMF1 (c.697C>T, p.Arg233Ter). The activities of lipoprotein lipase (LPL) and hepatic lipase
in post-heparin plasma were not abolished but reduced. The use of pemafibrate decreased
plasma TG levels with a concomitant increase in LPL activity.
HTG in childhood or early pregnancy is commonly assumed to be polygenic in origin
but should be regarded as a feature suggestive of monogenic hyperchylomicronemia.
Adequate TG monitoring and dietary fat restriction should be implemented to prevent
potentially lethal events of pancreatitis.
Keywords
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References
- Severe hypertriglyceridemia in pregnancy.J Clin Endocrinol Metab. 2012; 97: 2589-2596https://doi.org/10.1210/jc.2012-1250
- Review of the clinical development of alipogene tiparvovec gene therapy for lipoprotein lipase deficiency.Atheroscler Suppl. 2010; 11: 55-60https://doi.org/10.1016/j.atherosclerosissup.2010.03.004
- Plasma lipoproteins including high density lipoprotein subfractions during normal pregnancy.Obstet Gynecol. 1985; 66: 468-472
- Current diagnosis and management of primary chylomicronemia.J Atheroscler Thromb. 2021; 28: 883-904https://doi.org/10.5551/jat.RV17054
- Emergent triglyceride-lowering therapy with early high-volume hemofiltration against low-molecular-weight heparin combined with insulin in hypertriglyceridemic pancreatitis: a prospective randomized controlled trial.J Clin Gastroenterol. 2016; 50: 772-778https://doi.org/10.1097/MCG.0000000000000552
- Identification of unique lipoprotein subclasses for visceral obesity by component analysis of cholesterol profile in high-performance liquid chromatography.Arterioscler Thromb Vasc Biol. 2005; 25: 578-584https://doi.org/10.1161/01.ATV.0000155017.60171.88
- An automated method for measuring lipoprotein lipase and hepatic triglyceride lipase activities in post-heparin plasma.Clin Chim Acta. 2018; 487: 54-59https://doi.org/10.1016/j.cca.2018.09.022
- Acute pancreatitis in pregnancy: an overview.Eur J Obstet Gynecol Reprod Biol. 2011; 159: 261-266https://doi.org/10.1016/j.ejogrb.2011.07.037
- Severe dyslipidemia in pregnancy: the role of therapeutic apheresis.Transfus Apher Sci. 2015; 53: 283-287https://doi.org/10.1016/j.transci.2015.11.008
- Genetic variants associated with gestational hypertriglyceridemia and pancreatitis.PLoS ONE. 2015; 10e0129488https://doi.org/10.1371/journal.pone.0129488
- Estrogen induced hypertriglyceridemia in an apolipoprotein AV deficient patient.J Intern Med. 2008; 263: 107-108https://doi.org/10.1111/j.1365-2796.2007.01889.x
- APOA5 Q97X mutation identified through homozygosity mapping causes severe hypertriglyceridemia in a Chilean consanguineous family.BMC Med Genet. 2012; 13: 106https://doi.org/10.1186/1471-2350-13-106
- Involvement of a homozygous exon 6 deletion of LMF1 gene in intermittent severe hypertriglyceridemia.J Clin Lipidol. 2020; 14: 756-761https://doi.org/10.1016/j.jacl.2020.09.004
- Mutations in LMF1 cause combined lipase deficiency and severe hypertriglyceridemia.Nat Genet. 2007; 39: 1483-1487https://doi.org/10.1038/ng.2007.24
- Novel LMF1 nonsense mutation in a patient with severe hypertriglyceridemia.J Clin Endocrinol Metab. 2009; 94: 4584-4590https://doi.org/10.1210/jc.2009-0594
- Detailed analysis of lipolytic enzymes in a Japanese woman of familial lipoprotein lipase deficiency - Effects of pemafibrate treatment.Clin Chim Acta. 2020; 510: 216-219https://doi.org/10.1016/j.cca.2020.07.031
- Lipid metabolism in pregnancy and its consequences in the fetus and newborn.Endocrine. 2002; 19: 43-55https://doi.org/10.1385/ENDO:19:1:43
- Dissociation of apoprotein B and triglyceride production in very-low-density lipoproteins.Am J Physiol. 1980; 239: E354-E362https://doi.org/10.1152/ajpendo.1980.239.5.E354
- Overproduction of very low-density lipoproteins is the hallmark of the dyslipidemia in the metabolic syndrome.Arterioscler Thromb Vasc Biol. 2008; 28: 1225-1236https://doi.org/10.1161/ATVBAHA.107.160192
- Critical role of SREBP-1c large-VLDL pathway in environment-induced hypertriglyceridemia of Apo AV deficiency.Arterioscler Thromb Vasc Biol. 2019; 39: 373-386https://doi.org/10.1161/ATVBAHA.118.311931
- Identification and diagnosis of patients with familial chylomicronaemia syndrome (FCS): expert panel recommendations and proposal of an “FCS score.Atherosclerosis. 2018; 275: 265-272https://doi.org/10.1016/j.atherosclerosis.2018.06.814
- Genetic testing in dyslipidemia: a scientific statement from the national lipid association.J Clin Lipidol. 2020; 14: 398-413https://doi.org/10.1016/j.jacl.2020.04.011
Article info
Publication history
Published online: March 21, 2023
Accepted:
March 14,
2023
Received:
September 28,
2022
Publication stage
In Press Journal Pre-ProofFootnotes
Declaration of Competing Interest: The authors declare that there are no conflicts of interest that could be perceived as prejudicing the impartiality of the reported research.
Authors’ contributions: Writing the manuscript: M.T. and H.O.; Conceptualization and methodology: M.T. and H.O.; Data acquisition, investigation, and data analysis: M.T., S.T., H.I., T.Y., S.O., and H.O.; Editing the manuscript: M.T., S.T., H.I., T.Y., S.O., and H.O. All authors have read and approved the final manuscript.
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© 2023 National Lipid Association. Published by Elsevier Inc. All rights reserved.
