Department of Clinical Laboratory Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Department of Pediatrics, Takarazuka City Hospital, Takarazuka, Japan.
J Clin Endocrinol Metab. 2018 Jul 1;103(7):2488-2497. doi: 10.1210/jc.2017-02664.
Citrin-deficient infants present neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), which resolves at 12 months. Thereafter, they have normal liver function associated with hypercholesterolemia, and a preference for lipid-rich carbohydrate-restricted diets. However, some develop adult-onset type II citrullinemia, which is associated with metabolic abnormalities.
To identify the causes of hypercholesterolemia in citrin-deficient children post-NICCD.
We determined the concentrations of sterol markers of cholesterol synthesis, absorption, and catabolism by liquid chromatography-electrospray ionization-tandem mass spectrometry and evaluated serum lipoprotein profiles.
Twenty citrin-deficient children aged 5 to 13 years and 37 age-matched healthy children.
None.
Relationship between serum lipoproteins and sterol markers of cholesterol metabolism.
The citrin-deficient group had a significantly higher high-density lipoprotein cholesterol (HDL-C) concentration than did the control group (78 ± 11 mg/dL vs 62 ± 14 mg/dL, P < 0.001), whereas the two groups had similar low-density lipoprotein cholesterol and triglyceride concentrations. The concentrations of markers of cholesterol synthesis (lathosterol and 7-dehydrocholesterol) and bile acids synthesis (7α-hydroxycholesterol and 27-hydroxycholesterol) were 1.5- to 2.8-fold and 1.5- to 3.9-fold, respectively, higher in the citrin-deficient group than in the control group. The concentration of 24S-hydroxycholesterol, a marker of cholesterol catabolism in the brain, was 2.5-fold higher in the citrin-deficient group. In both groups, the HDL-C concentration was significantly positively correlated with that of 27-hydroxycholesterol, the first product of the alternative bile acid synthesis pathway.
HDL-C and sterol marker concentrations are elevated in citrin-deficient children post-NICCD. Moreover, cholesterol synthesis and elimination are markedly enhanced in the liver and brain of citrin-deficient children.
Citrin 缺乏症婴儿会出现由 Citrin 缺乏引起的新生儿肝内胆汁淤积症（NICCD），这种病症会在 12 个月时得到缓解。此后，他们的肝功能正常，但伴有高胆固醇血症，以及偏爱富含脂质、限制碳水化合物的饮食。然而，一些人会发展为成年期 II 型瓜氨酸血症，这与代谢异常有关。
确定 NICCD 后 Citrin 缺乏症儿童高胆固醇血症的原因。
我们通过液相色谱-电喷雾电离-串联质谱法测定胆固醇合成、吸收和分解代谢的甾醇标志物浓度，并评估血清脂蛋白谱。
20 名年龄在 5 至 13 岁的 Citrin 缺乏症儿童和 37 名年龄匹配的健康儿童。
无。
血清脂蛋白与胆固醇代谢甾醇标志物之间的关系。
Citrin 缺乏组的高密度脂蛋白胆固醇（HDL-C）浓度明显高于对照组（78 ± 11 mg/dL 比 62 ± 14 mg/dL，P < 0.001），而两组的低密度脂蛋白胆固醇和甘油三酯浓度相似。胆固醇合成标志物（羊毛甾醇和 7-脱氢胆固醇）和胆汁酸合成标志物（7α-羟胆固醇和 27-羟胆固醇）的浓度在 Citrin 缺乏组分别是对照组的 1.5-2.8 倍和 1.5-3.9 倍。胆固醇在大脑中的分解代谢标志物 24S-羟胆固醇的浓度在 Citrin 缺乏组是对照组的 2.5 倍。在两组中，HDL-C 浓度与替代胆汁酸合成途径的第一个产物 27-羟胆固醇的浓度均呈显著正相关。
NICCD 后 Citrin 缺乏症儿童的 HDL-C 和甾醇标志物浓度升高。此外，Citrin 缺乏症儿童的肝脏和大脑中胆固醇的合成和消除明显增强。
