Central Oklahoma Early Detection Center, Lipidology and Cardiometabolic Clinic, 1227 East 9th Street, Edmond, OK 73034, USA; The University of Oklahoma College of Medicine, 941 Stanton L. Young Boulevard, Oklahoma City, Oklahoma 73104, USA.
Boston Heart Diagnostics, Framingham, MA, USA; Lipid Metabolism Laboratory, Human Nutrition Research Center on Aging at Tufts University and Tufts University School of Medicine, Boston, MA, USA.
J Clin Lipidol. 2014 Mar-Apr;8(2):223-30. doi: 10.1016/j.jacl.2013.11.005. Epub 2013 Dec 11.
A kindred affected with fish eye disease (FED) from Oklahoma is reported. Two probands with corneal opacification had mean levels of high-density lipoprotein (HDL) cholesterol (C), apolipoprotein (apo) A-I, and apoA-I in very large alpha-1 HDL particles that were 9%, 17%, and 5% of normal, whereas their parents and 1 sibling had values that were 61%, 77%, and 72% of normal. The probands had no detectable lipoprotein-X, and had mean low-density lipoprotein cholesterol (LDL-C) and triglyceride levels that were elevated. Their mean lecithin cholesterol acyltransferase (LCAT) activities, cholesterol esterification rates, and free cholesterol levels were 8%, 42%, and 258% of normal, whereas their parents and 1 sibling had values that were 55%, 49%, and 114% of normal. The defect was due to 1 common variant in the LCAT gene in exon 1: c101t causing a proline34leucine substitution and a novel mutation c1177t causing a threonine37methionine substitution, with the former variant being found in the father and 1 sibling, and the latter mutation being found in the mother, and both mutations being present in the 2 probands. FED is distinguished from familial LCAT deficiency (FLD) by the lack of anemia, splenomegaly, and renal insufficiency as well as normal or increased LDL-C. Both FLD and FED cases have marked HDL deficiency and corneal opacification, and FED cases may have premature coronary heart disease in contrast to FLD cases. Therapy, using presently available agents, in FED should be to optimize LDL-C levels, and 1 proband responded well to statin therapy. The investigational use of human recombinant LCAT as an enzyme source is ongoing.
报告了来自俄克拉荷马州的一位患有鱼眼病（FED）的患者。两名角膜混浊的先证者的高密度脂蛋白（HDL）胆固醇（C）、载脂蛋白（apo）A-I 和 apoA-I 的水平非常高，在超大 alpha-1 HDL 颗粒中的含量分别为正常水平的 9%、17%和 5%，而他们的父母和 1 个兄弟姐妹的水平分别为正常水平的 61%、77%和 72%。先证者没有检测到脂蛋白-X，且低密度脂蛋白胆固醇（LDL-C）和甘油三酯水平升高。他们的卵磷脂胆固醇酰基转移酶（LCAT）活性、胆固醇酯化率和游离胆固醇水平分别为正常水平的 8%、42%和 258%，而他们的父母和 1 个兄弟姐妹的水平分别为正常水平的 55%、49%和 114%。该缺陷是由于 LCAT 基因外显子 1 中的 1 个常见变异引起的：c101t 导致脯氨酸 34 亮氨酸取代和新的突变 c1177t 导致苏氨酸 37 蛋氨酸取代，前者变异存在于父亲和 1 个兄弟姐妹中，后者突变存在于母亲中，两个突变均存在于 2 个先证者中。FED 与家族性 LCAT 缺乏症（FLD）的区别在于无贫血、脾肿大和肾功能不全以及正常或升高的 LDL-C。FLD 和 FED 病例均有明显的 HDL 缺乏和角膜混浊，而 FED 病例可能比 FLD 病例更早发生冠心病。目前可用药物的治疗应该是优化 LDL-C 水平，1 例先证者对他汀类药物治疗反应良好。正在进行用重组人 LCAT 作为酶源的研究性治疗。
