Citrin缺陷引起的新生儿肝内胆汁淤积症两例临床特点及家系基因分析

Clinical Features and Pedigreed Gene Analysis of Neonates with Intrahepatic Cholestasis Caused by Citrin Deficiency:Two Cases Report

目的探讨2例Citrin缺陷引起的新生儿肝内胆汁淤积症患儿的临床特点,了解其家系基因突变情况。方法在2例患儿及其父母血样中提取DNA,根据文献中报道的12种已知突变在基因上的分布位置,将其所在区域分成6个片段扩增,扩增后行琼脂糖凝胶电泳,纯化后直接测序,确定患儿及其父母基因类型。结果 2例患儿均因皮肤黄染入院;入院查体:皮肤、巩膜黄染;实验室检查:转氨酶升高,胆红素双向升高,血常规提示贫血,凝血功能正常,甲胎蛋白升高。例1患儿为851del4/851del4纯合突变,父母均为携带者;例2患儿为[Ⅰ]851del4/[Ⅱ]IVS11+IG>A的复合变异,父母均为携带者。2例患儿经特殊饮食配方喂养,预后良好。结论 2例患儿的父母均为SLC25A13基因突变携带者,其中例1患儿为851del4纯合突变,例2患儿为[Ⅰ]851del4/[Ⅱ]IVS11+IG>A杂合突变。

Objective To explore the clinical features of two neonates with intrahepatic cholestasis caused by Citrin deficiency and investigate their pedigreed gene mutation. Methods DNA was extracted from the blood samples of the two neo- nates and their parents. PCR amplification was performed according to the genetic sites of 12 confirmed mutations reported, next agarose gel electrophoresis was performed, and then after the PCR products were purified, automated DNA sequencing was con- ducted to detect the genotype of the neonates and their parents. Results The two neonate patients were admitted because of jaundice. On admission physical examination showed ieteric skin and selera. Laboratory examination revealed elevated transami- nase ; Elevation of both direct and indirect bilirubin ; Anemia in blood routine ; Normal coagulation function; And elevated alpha fetal protein. The first neonate had 851de14 homozygotes, and his parents were carrier. The second neonate had [ I ] 851de14/ [ II ] IVS11 ＋ IG 〉 A heterozygotes, and his parents were carrier. The two neonate patients were on a special diet so they had a favorable prognosis. Conclusion The parents of the two neonates were SLC25A13 genie mutation carrier. One was 851de14 ho- mozygotes, and the other was [ I ] 851de14/ [ II] IVSll ＋IG 〉A heterozygotes.