Sustaining hypercitrullinemia, hypercholesterolemia and augmented oxidative stress in Japanese children with aspartate/glutamate carrier isoform 2-citrin-deficiency even during the silent period
Sustaining hypercitrullinemia, hypercholesterolemia and augmented oxidative stress in Japanese children with aspartate/glutamate carrier isoform 2-citrin-deficiency even during the silent period
复制标题
DOI：
10.1016/j.ymgme.2009.01.009
复制
发表时间：
2009-05-01
影响因子：
3.8
通讯作者：
Yorifuji, Tohru
中科院分区：
文献类型：
--
作者：
Nagasaka, Hironori;Okano, Yoshiyuki;Yorifuji, Tohru
由瓜氨酸缺乏引起的新生儿肝内胆汁淤积症（NICCD）表现出多种代谢异常，如尿素循环功能障碍以及瓜氨酸血症、半乳糖血症和抑制性肝细胞生成。这种异常现象在出生后的第一年就消失了。然而，沉默期的代谢特征仍然未知。我们分析了20名1-10岁的无症状天冬氨酸/谷氨酸载体亚型2-桔黄素缺乏症儿童的氧化应激标志物和氨基酸、碳水化合物和脂质的概况，这些儿童的检查显示肝功能正常。尽管血氨水平正常，但与健康儿童相比，受影响的儿童血液中的鸟氨酸（p < 0.001）和瓜氨酸（p < 0.01）--参与尿素循环的氨基酸--水平较高。血液中的亚硝酸盐/硝酸盐，一氧化氮（NO）的代谢产物，和不对称二甲基精氨酸抑制NO生产精氨酸之间没有差异。血糖，半乳糖，丙酮酸，和乳酸水平禁食4-5小时后，这些组之间没有差异，但受影响的组显示出显着较高的乳酸丙酮酸比。受影响组的低密度和高密度脂蛋白胆固醇水平是对照组的1.5倍。患病儿童血浆氧化低密度脂蛋白明显升高;他们的尿液氧化应激标志物如8-羟基-2 '-脱氧鸟苷和丙烯醛-赖氨酸水平显着高于对照组。这项研究的结果表明，即使在沉默期，持续的高瓜氨酸血症，高胆固醇血症，并增加了氧化应激与瓜氨酸缺乏症的儿童。(C)2009 Elsevier Inc. All rights reserved.
Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) shows diverse metabolic abnormalities such as urea cycle dysfunction together with citrullinemia, galactosemia, and suppressed gluconeogenesis. Such abnormalities apparently resolve during the first year of life. However, metabolic profiles of the silent period remain unknown. We analyzed oxidative stress markers and profiles of amino acids, carbohydrates, and lipids in 20 asymptomatic children with aspartate/glutamate carrier isoform 2-citrin-deficiency aged 1-10 years, for whom tests showed normal liver function. Despite normal plasma ammonia levels, the affected children showed higher blood levels of ornithine (p < 0.001) and citrulline (p < 0.01)-amino acids involved in the urea cycle-than healthy children. Blood levels of nitrite/nitrate, metabolites of nitric oxide (NO), and asymmetric dimethylarginine inhibiting NO production from arginine were not different between these two groups. Blood glucose, galactose, pyruvate, and lactate levels after 4-5 h fasting were not different between these groups, but the affected group showed a significantly higher lactate to pyruvate ratio. Low-density and high-density lipoprotein cholesterol levels in the affected group were 1.5 times higher than those in the controls. Plasma oxidized low-density lipoprotein apparently increased in the affected children; their levels of urinary oxidative stress markers such as 8-hydroxy-2'-deoxyguanosine and acrolein-lysine were significantly higher than those in the controls. Results of this study showed, even during the silent period, sustained hypercitrullinemia, hypercholesterolemia, and augmented oxidative stress in children with citrin deficiency. (C) 2009 Elsevier Inc. All rights reserved.