疑难病研究——钠牛磺胆酸共转运多肽缺陷病表现为婴儿早期胆汁淤积性黄疸

发布时间：2018-09-13 05:47

【摘要】：钠牛磺胆酸共转运多肽(NTCP)缺陷病是由于SLC10A1基因突变,肝细胞基侧膜转运蛋白NTCP的胆汁酸盐摄取功能受损面形成的一种遗传代谢病。该文患儿因发现皮肤巩膜黄染5.5个月(生后第2天出现黄疸)、肝功能异常4月余就诊。肝功能示总胆红素、直接胆红素、间接胆红素和总胆汁酸均明显上升。曾按胆汁淤积性肝病内科治疗,疗效欠佳,于2月龄时行剖腹探查+胆囊造瘘+胆道造影术,术中发现胆汁粘稠但胆道通畅。术后黄疸消退,但转氨酶和总胆汁酸水平逐渐升高。患儿母亲亦发现有轻微高胆汁酸血症。患儿未予特殊治疗,目前已门诊随访两年余,转氨酶逐渐恢复正常,总胆汁酸波动于23.3~277.7μmol/L。患儿2岁9个月行SLC10A1基因分析,结果证实患儿及其母均为致病性变异c.800CT(p.S267F)的纯合子,从而确诊NTCP缺陷病。该研究提示,NTCP缺陷病成人患者仅有轻微高胆汁酸血症,但儿科患者胆汁酸升高明显而且持续,且部分病例在婴儿早期可表现为胆汁淤积性黄疸。
[Abstract]:Sodium taurocholic acid co-transporter polypeptide (NTCP) deficiency is a genetic metabolic disease caused by SLC10A1 gene mutation and impaired bile acid uptake function of hepatocyte basal membrane transporter NTCP. The children were diagnosed with scleral yellow staining 5.5 months after birth (jaundice on the second day of life) and liver function abnormality for 4 months. Liver function showed that total bilirubin, direct bilirubin, indirect bilirubin and total bile acid were significantly increased. The cholestatic liver disease was treated by internal medicine, the curative effect was not good, the choledochotomy was performed at 2 months old. The bile was thick but the bile duct was unobstructed during the operation. Jaundice subsided after operation, but the levels of transaminase and total bile acid increased gradually. The mother of the child also found slight hyperbile acidemia. No special treatment was given to the children. At present, they have been followed up for more than two years. The total bile acids fluctuate at 23.3n 277.7 渭 mol/L. the aminotransferase gradually returns to normal. SLC10A1 gene analysis was performed at 2 years and 9 months in children. The results confirmed that the children and their mothers were homozygotes of pathogenicity variant c.800CT (p.S267F) and thus diagnosed NTCP deficiency disease. This study suggests that there is only slight hyperbilirubinemia in adult patients with NTCP deficiency, but the increase in bile acid in pediatric patients is significant and persistent, and some cases may show cholestatic jaundice in early infantile stage.
【作者单位】：暨南大学附属第一医院儿科;
【基金】：国家自然科学基金(81270957,81570793)
【分类号】：R725.7

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