Semmler Georg, Baumgartner Clemens, Metz Matthäus, Gensluckner Sophie, Habisch Hansjörg, Hofer Hannah, März Winfried, Offner Felix, Völkerer Andreas, Petrenko Oleksandr, Wernly Bernhard, Draxler-Dworzak Sophie, Neyer Manuela, Nigmann Charlotte, Greber-Platzer Susanne, Esterbauer Harald, Madl Tobias, Aigner Elmar, Scherer Thomas, Datz Christian
Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
Centre for Liver Research, Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark.
J Clin Endocrinol Metab. 2025 Mar 3. doi: 10.1210/clinem/dgaf131.
Tangier disease (TD) is a rare, autosomal recessive genetic disorder associated with a deficiency in cellular cholesterol export leading to cholesterol accumulation in peripheral tissues. With approximately 150 described cases, the disease is significantly understudied, and the clinical presentation appears to be heterogenous.
To investigate the phenotype and lipid metabolism in TD.
Multicenter cohort study.
Four patients with TD.
Nuclear magnetic resonance (NMR)-based lipidomic and metabolomic analyses were performed in patients with TD and healthy controls.
While showing similar laboratory patterns with respect to high-density lipoprotein depletion, the clinical phenotypes of four TD patients were heterogenous with two patients diagnosed at 47 and 72 years having predominantly gastrointestinal and neurological phenotypes. Two previously undescribed variants (c.2418G>A, c.5055.del) were reported.Apart from pathognomonic changes in HDL composition, NMR spectroscopy revealed an increased abundance of VLDL with higher total lipid and cholesterol concentrations, pointing towards an impaired clearance of triglyceride-rich lipoproteins. Increased triglyceride-rich IDL supports impaired hepatic lipase activity, together with a CETP-mediated increase in LDL-triglycerides at higher abundance of large LDL subtypes and decreased small dense LDL.The lipid composition of HDL particles and LDL-1/LDL-4 remained the strongest differentiating factors as compared to healthy controls.
Clinical phenotypes of TD can be heterogeneous including gastrointestinal and neurological manifestations. Impaired triglyceride-rich lipoprotein clearance and hepatic lipase activity could be a pathophysiological hallmark of TD.
丹吉尔病（TD）是一种罕见的常染色体隐性遗传病，与细胞胆固醇输出缺陷有关，导致外周组织中胆固醇蓄积。该疾病仅有约150例已报道病例，研究明显不足，且临床表现似乎具有异质性。
研究丹吉尔病的表型和脂质代谢。
多中心队列研究。
4例丹吉尔病患者。
对丹吉尔病患者和健康对照进行基于核磁共振（NMR）的脂质组学和代谢组学分析。
虽然4例丹吉尔病患者在高密度脂蛋白缺乏方面表现出相似的实验室特征，但其临床表型具有异质性，2例分别在47岁和72岁确诊的患者主要表现为胃肠道和神经学表型。报告了2个此前未描述的变异（c.2418G>A，c.5055.del）。除了高密度脂蛋白组成的特征性变化外，核磁共振波谱显示极低密度脂蛋白丰度增加，总脂质和胆固醇浓度更高，表明富含甘油三酯脂蛋白的清除受损。富含甘油三酯的中间密度脂蛋白增加支持肝脂酶活性受损，同时在大低密度脂蛋白亚型丰度较高时胆固醇酯转运蛋白介导低密度脂蛋白甘油三酯增加，小而密低密度脂蛋白减少。与健康对照相比，高密度脂蛋白颗粒和低密度脂蛋白-1/低密度脂蛋白-4的脂质组成仍然是最主要的鉴别因素。
丹吉尔病的临床表型可以是异质性的，包括胃肠道和神经学表现。富含甘油三酯脂蛋白清除受损和肝脂酶活性受损可能是丹吉尔病的病理生理标志。
