Department of Endocrinology and Cardiovascular Disease Prevention, Assistance Publique-Hôpitaux de Paris, La Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France.
Department of Nutrition, Maladies Métaboliques et Endocrinologie, Hôpital Conception, Marseille, France.
Curr Atheroscler Rep. 2020 Aug 27;22(11):63. doi: 10.1007/s11883-020-00885-1.
Familial chylomicronemia syndrome (FCS) is a rare recessive genetic disorder often underdiagnosed with potentially severe clinical consequences. In this review, we describe the clinical and biological characteristics of the disease together with its main complication, i.e., acute pancreatitis. We focused the paper on new diagnostic tools, progress in understanding the role of two key proteins (apolipoprotein CIII (apo CIII) and angiopoietin-like3 (ANGPTL-3)), and new therapeutic options.
Recently, a new diagnostic tool has been proposed by European experts to help identify these patients. This tool with two recently identified parameters (low LDL and low body mass index) can help identify patients who should be genetically tested or who may have the disease when genetic testing is not available. FCS is caused by homozygous or compound heterozygous mutations of lipoprotein lipase, apolipoprotein C-II, apolipoprotein A-V, glycosylphosphatidylinositol anchored high-density lipoprotein-binding protein 1, and lipase maturation factor. Two proteins have been identified as important player in the metabolism of triglyceride-rich lipoprotein and its regulation. These two proteins are therapeutic target. Antisense oligonucleotide targeting apo CIII has been shown to significantly decrease triglyceride levels even in FCS and is the first available treatment for these patients. Further development might identify new compounds with reduced risk to develop severe thrombocytopenia. ANGPTL-3 inhibitors have not yet been tested in FCS patients but exert significant hypotriglyceridemic effect in the more frequent and less severe polygenic forms. Beyond these two new targets, microsomal triglyceride transfer protein (MTTP) inhibitors could also be part of the armamentarium, if on-going trials confirm their efficacy. New clinical tools and simple criteria can help select patients with possible FCS and identify patients who should have a genetic testing. Identifying patients with FCS is a major issue since these patients have a high risk to suffer severe episodes of acute pancreatitis and may now benefit from new therapeutic options including antisense oligonucleotide targeting apo CIII.
家族性乳糜微粒血症综合征（FCS）是一种罕见的常染色体隐性遗传性疾病，临床诊断率较低，可能导致严重的后果。本综述描述了该疾病的临床和生物学特征及其主要并发症，即急性胰腺炎。本文重点介绍了新的诊断工具、对两种关键蛋白（载脂蛋白 CIII（apo CIII）和血管生成素样蛋白 3（ANGPTL-3））作用的深入理解以及新的治疗选择。
最近，欧洲专家提出了一种新的诊断工具，以帮助识别这些患者。该工具使用两个最近确定的参数（低 LDL 和低体重指数）可以帮助识别应进行基因检测的患者，或在无法进行基因检测时，识别可能患有该疾病的患者。FCS 是由脂蛋白脂肪酶、载脂蛋白 C-II、载脂蛋白 A-V、糖基磷脂酰肌醇锚定高密度脂蛋白结合蛋白 1 和脂肪酶成熟因子的纯合子或复合杂合突变引起的。两种蛋白被确定为甘油三酯-rich 脂蛋白代谢及其调节的重要调控因子。这两种蛋白是治疗靶点。靶向 apo CIII 的反义寡核苷酸已被证明可显著降低甘油三酯水平，即使在 FCS 中也是如此，是这些患者的第一种可用治疗方法。进一步的开发可能会发现新的化合物，降低发生严重血小板减少症的风险。ANGPTL-3 抑制剂尚未在 FCS 患者中进行测试，但在更常见且不太严重的多基因形式中可显著降低甘油三酯水平。除了这两个新靶点之外，微粒体甘油三酯转移蛋白（MTTP）抑制剂也可能成为治疗手段之一，如果正在进行的试验证实其疗效。新的临床工具和简单的标准可以帮助选择可能患有 FCS 的患者，并识别应进行基因检测的患者。识别 FCS 患者是一个主要问题，因为这些患者有发生严重急性胰腺炎的高风险，现在可能受益于新的治疗选择，包括靶向 apo CIII 的反义寡核苷酸。
