The Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
The Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
J Clin Lipidol. 2023 May-Jun;17(3):327-331. doi: 10.1016/j.jacl.2023.03.005. Epub 2023 Mar 22.
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.
妊娠期高甘油三酯血症（HTG）引起的胰腺炎可导致母婴死亡。然而，其遗传基础尚未完全阐明，治疗策略也尚未建立。这里我们报告了一例妊娠相关 HTG 伴急性胰腺炎的 LMF1 新型纯合无义变异病例。我们的患者在儿童期即出现严重的 HTG，在非妊娠期通过饮食管理得到很好的控制，血浆甘油三酯（TG）水平约为 200mg/dL。在妊娠早期检查时发现乳糜样血浆，随后在妊娠晚期 TG 水平严重升高（10500mg/dL）导致胰腺炎。严格限制饮食脂肪（每天少于 4 克）可降低血浆 TG 水平并成功分娩。外显子组测序显示 LMF1 中存在一种新型纯合无义变异（c.697C>T，p.Arg233Ter）。肝素后血浆中脂蛋白脂肪酶（LPL）和肝脂肪酶的活性没有被消除，但降低了。使用 pemafibrate 可降低血浆 TG 水平，并同时增加 LPL 活性。儿童期或妊娠早期的 HTG 通常被认为是多基因遗传，但应被视为单基因高乳糜微粒血症的特征。应进行充分的 TG 监测和饮食脂肪限制，以预防胰腺炎的潜在致命事件。
