Abstract

Familial dysbetalipoproteinemia (type III hyperlipoproteinemia) is a potentially underdiagnosed inherited dyslipidemia associated with greatly increased risk of coronary and peripheral vascular disease. The mixed hyperlipidemia observed in this disorder usually responds well to appropriate medical therapy and lifestyle modification. Although there are characteristic clinical features such as palmar and tuberous xanthomata, associated with dysbetalipoproteinemia, they are not always present, and their absence cannot be used to exclude the disorder. The routine lipid profile cannot distinguish dysbetalipoproteinemia from other causes of mixed hyperlipidemia and so additional investigations are required for confident diagnosis or exclusion. A range of investigations that have been proposed as potential diagnostic tests are discussed in this review, but the definitive biochemical test for dysbetalipoproteinemia is widely considered to be beta quantification. Beta quantification can determine the presence of “β-VLDL” in the supernatant following ultracentrifugation and whether the VLDL cholesterol to triglyceride ratio is elevated. Both features are considered hallmarks of the disease. However, beta quantification and other specialist tests are not widely available and are not high-throughput tests that can practically be applied to all patients with mixed hyperlipidemia. Using apolipoprotein B (as a ratio either to total or non-HDL cholesterol or as part of a multi-step algorithm) as an initial test to select patients for further investigation is a promising approach. Several studies have demonstrated a high degree of diagnostic sensitivity and specificity using these approaches and apolipoprotein B is a relatively low-cost test that is widely available on high-throughput platforms. Genetic testing is also important in the diagnosis, but it should be noted that most individuals with an E₂/₂ genotype do not suffer from remnant hyperlipidemia and around 10% of familial dysbetalipoproteinemia cases are caused by rarer, autosomal dominant mutations in APOE that will only be detected if the gene is fully sequenced. Wider implementation of diagnostic pathways utilizing apo B could lead to more rational use of specialist investigations and more consistent detection of patients with dysbetalipoproteinemia. Without the application of a consistent evidence-based approach to identifying dysbetalipoproteinemia, many cases are likely to remain undiagnosed.

摘要

家族性高脂蛋白血症（III型高脂蛋白血症）是一种潜在的未被诊断的遗传性血脂异常，与冠状动脉和周围血管疾病的风险大大增加有关。在这种疾病中观察到的混合性高脂血症通常对适当的药物治疗和生活方式改变反应良好。尽管存在特征性的临床特征，例如与脂蛋白脂蛋白异常相关的掌状和结节状黄单胞菌，但它们并不总是存在，并且它们的缺乏不能用来排除疾病。常规的脂质分布无法将dysbetalipoproteinemia与其他混合性高脂血症原因区分开，因此需要进一步的研究以确保诊断或排除。这篇评论讨论了一系列建议作为潜在诊断测试的研究，但是针对dysbeta脂蛋白血症的确定性生化测试被广泛认为是beta量化。Beta定量可以确定超速离心后上清液中“β-VLDL”的存在以及VLDL胆固醇与甘油三酸酯的比率是否升高。这两个特征均被认为是该疾病的标志。但是，β定量和其他专业测试尚不广泛，也不是可实际用于所有混合性高脂血症患者的高通量测试。使用载脂蛋白B（作为总HDL或非HDL胆固醇的比率或作为多步算法的一部分）作为初始测试来选择患者进行进一步研究的方法是一种很有前途的方法。多项研究表明，使用这些方法具有高度的诊断敏感性和特异性，载脂蛋白B是一种相对低成本的测试，可在高通量平台上广泛使用。遗传检测在诊断中也很重要，但应注意，大多数患有E的个体₂ / ₂基因型不从剩余患有高脂血症和家族性异常β脂蛋白血症病例有10％左右是由罕见引起的，常染色体显性遗传突变APOE如果基因完全测序将只检测。利用载脂蛋白B的诊断途径的更广泛实施可以导致更合理地利用专家研究，以及对dysbeta脂蛋白血症患者进行更一致的检测。如果没有采用一致的基于证据的方法来鉴定dysbeta脂蛋白血症，许多病例很可能仍无法诊断。