Yao J K, Herbert P N, Fredrickson D S, Ellefson R D, Heinen R J, Forte T, Dyck P J
J Neuropathol Exp Neurol. 1978 Mar-Apr;37(2):138-54. doi: 10.1097/00005072-197803000-00003.
The chemical composition of the major classes of lipids were evaluated in the plasma and in various other tissues of a 68-year-old woman with a syringomyelia-like syndrome affecting cranial, cervical and brachial regions. No tonsillar abnormalities were apparent on visual examination of the oropharynx but the absence of alpha-lipoproteins on serum lipoprotein electrophoresis prompted the tentative diagnosis of Tangier disease. The diagnosis was confirmed by lipid, lipoprotein and apolipoprotein analyses of the plasma. The plasma cholesterol was low (93-113 mg/dl) and the triglyceride concentration normal (133-160 mg/dl). The very low density lipoproteins had normal chemical composition and morphology, but migrated with beta rather than pre-beta mobility on paper electrophoresis. Low density lipoproteins were deficient in cholesteryl esters and enriched in triglycerides; their electrophoretic mobility and morphology were normal. A small amount of high density lipoprotein (approximately 1.4 mg/dl) was recovered from the plasma. This contained few particles of the size of normal high density lipoprotein and polyacrylamide gel electrophoresis of the lipid-free protein demonstrated a disproportionate increase in the A-II apolipoprotein. All of these abnormalities are consistent with Tangier disease. The serum concentration of glycosphingolipids was approximately 40% lower than normal, with the most marked reductions in the glucosylceramide (GL-1a) and trihexosylceramide (GL-3a) fractions. The relative quantity of long chain fatty acids (23 or more carbons) in serum sphingomyelin was reduced about 38% of that in control sera. Serum lecithin:cholesterol acyltransferase (EC 2.3.1.43; LCAT) activity was 25% of normal and the reduced activity was shown not to be related to a change of enzyme specificity or to a lack of appropriate substrate. These findings are likely related to the HDL deficiency which characterizes Tangier disease. A biopsy sample of apparently normal tonsil contained three to four times the normal amount of cholesterol, and the increase was due entirely to abnormal quantities of cholesteryl esters. Of great interest was the chemical documentation of increased cholesteryl esters in a nerve biopsy specimen. These findings indicate that the neurologic as well as the reticuloendothelial manifestations of Tangier disease may be related to cholesteryl ester accumulation. Lipoprotein profiles, their triglyceride and cholesterol concentration, and LCAT activity were obtained on the plasma of 7 closely related members of the kinship. None of these relatives were found to have the biochemical derangement of Tangier disease.
对一名68岁患有影响颅、颈和臂部区域的类脊髓空洞症综合征的女性的血浆及其他多种组织中的主要脂质类别进行了化学成分评估。口咽部视诊未发现扁桃体异常，但血清脂蛋白电泳显示缺乏α-脂蛋白，提示初步诊断为丹吉尔病。血浆脂质、脂蛋白和载脂蛋白分析证实了该诊断。血浆胆固醇水平较低（93 - 113毫克/分升），甘油三酯浓度正常（133 - 160毫克/分升）。极低密度脂蛋白的化学成分和形态正常，但在纸上电泳时迁移至β区而非前β区。低密度脂蛋白胆固醇酯缺乏且甘油三酯富集；其电泳迁移率和形态正常。从血浆中回收了少量高密度脂蛋白（约1.4毫克/分升）。其中正常大小的高密度脂蛋白颗粒很少，无脂蛋白质的聚丙烯酰胺凝胶电泳显示A-II载脂蛋白不成比例增加。所有这些异常均与丹吉尔病相符。糖鞘脂的血清浓度比正常水平低约40%，其中葡糖神经酰胺（GL-1a）和三己糖神经酰胺（GL-3a）部分降低最为明显。血清鞘磷脂中长链脂肪酸（23个或更多碳原子）的相对含量约为对照血清的38%。血清卵磷脂胆固醇酰基转移酶（EC 2.3.1.43；LCAT）活性为正常水平的25%，且活性降低与酶特异性改变或缺乏合适底物无关。这些发现可能与丹吉尔病的高密度脂蛋白缺乏有关。一个看似正常的扁桃体活检样本中的胆固醇含量是正常量的三到四倍，且增加完全是由于胆固醇酯数量异常。神经活检标本中胆固醇酯增加的化学证据非常有趣。这些发现表明，丹吉尔病的神经及网状内皮系统表现可能与胆固醇酯积累有关。对该家族7名密切相关成员的血浆进行了脂蛋白谱、甘油三酯和胆固醇浓度以及LCAT活性检测。这些亲属均未发现有丹吉尔病的生化紊乱。
