Département d'Endocrinologie, Diabétologie et Nutrition, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Paris, France; Institute of Cardiometabolism and Nutrition, Paris, France; Université Paris-Diderot, Paris 7, Paris, France.
Institute of Cardiometabolism and Nutrition, Paris, France; Service de Biochimie endocrinienne et oncologique, Centre de Génétique Moléculaire et Chromosomique, AP-HP, Hôpital de la Pitié, Paris, France; Dyslipidemia and Atherosclerosis Research Unit, INSERM-UMRS 939, Hôpital de la Pitie, Paris, France.
Atherosclerosis. 2014 May;234(1):162-8. doi: 10.1016/j.atherosclerosis.2014.02.030. Epub 2014 Mar 11.
Phytosterolemia is a rare autosomal recessive disorder characterized by dramatically elevated circulating levels of plant sterols (PS). Phytosterolemia is believed to be responsible for severe premature atherosclerosis. The clinical, biological and molecular genetic features of 5 patients with phytosterolemia and transient severe hypercholesterolemia challenge this hypothesis.
Our patients were referred for suspected homozygous familial hypercholesterolemia. Despite the phenotype, this diagnosis was invalidated and phytosterolemia was confirmed by the identification of mutations in the ABCG5/ABCG8 transporter complex. Plasma PS were analyzed with a mass spectrometric-gas chromatographic procedure. Vascular status was assessed with carotid ultrasonography and completed (for 4 of the 5 patients) with femoral ultrasonography; additional examinations of cardiovascular status included a stress test, determination of coronary calcium score, echocardiography, non-invasive assessment of endothelium-dependent dilatation and coronarography.
The 5 patients displayed markedly elevated levels of both β-sitosterol and campesterol (15-30 fold higher than normal values). However, none displayed significant signs of infraclinical premature atherosclerosis (respectively at the ages of 32, 27, 29, 11 and 11 years). All patients were characterized by very high levels of total (>450 mg/dl) and LDL-cholesterol (>350 mg/dl) at diagnosis which decreased markedly on dietary intervention alone. Treatment with cholestyramine or Ezetimibe ± atorvastatin normalized cholesterol levels, although plasma PS concentrations remained elevated.
The clinical and biological characteristics of our patients, considered together with reports of cases which equally lack CVD, support the contention that the premature atherosclerosis associated with phytosterolemia in some patients may be due at least in part to mechanisms independent of elevated circulating phytosterol levels.
植物甾醇血症是一种罕见的常染色体隐性遗传病，其特征是循环植物甾醇（PS）水平显著升高。植物甾醇血症被认为是导致严重早发性动脉粥样硬化的原因。5 名植物甾醇血症和短暂性重度高胆固醇血症患者的临床、生物学和分子遗传学特征对这一假说提出了挑战。
我们的患者因疑似纯合家族性高胆固醇血症而被转介。尽管表型如此，但该诊断被否定，并通过鉴定 ABCG5/ABCG8 转运体复合物中的突变来确认植物甾醇血症。使用质谱-气相色谱程序分析血浆 PS。通过颈动脉超声检查和（5 名患者中的 4 名）股动脉超声检查评估血管状况；心血管状况的其他检查包括应激试验、冠状动脉钙评分测定、超声心动图、内皮依赖性舒张的非侵入性评估和冠状动脉造影。
5 名患者β-谷甾醇和菜油甾醇水平显著升高（比正常值高 15-30 倍）。然而，没有一名患者显示出亚临床早发性动脉粥样硬化的明显迹象（分别在 32、27、29、11 和 11 岁时）。所有患者在诊断时总胆固醇（>450mg/dl）和 LDL 胆固醇（>350mg/dl）水平非常高，仅通过饮食干预即可显著降低。单独使用考来烯胺或依折麦布+阿托伐他汀治疗可使胆固醇水平正常化，尽管血浆 PS 浓度仍升高。
我们患者的临床和生物学特征，以及同样缺乏 CVD 的病例报告，共同支持这样一种观点，即某些患者与植物甾醇血症相关的早发性动脉粥样硬化可能至少部分归因于与升高的循环植物甾醇水平无关的机制。
