疑难病研究—citrin缺陷导致的新生儿肝内胆汁淤积症  

A difficult and complicated case study: neonatal intrahepatic cholestasis caused by citrin deficiency

作　　者：宋元宗[1] 郝虎[1] 牛饲美晴[2] 柳国胜[1] 肖昕[1] 佐伯武顿[2] 小林圭子[2] 王自能[3] 

机构地区：[1]暨南大学附属第一医院儿科,广东广州510632 [2]日本鹿儿岛大学分子代谢和生化遗传学系 [3]暨南大学医学院妇产科教研室,广东广州510632

出　　处：《中国当代儿科杂志》2006年第2期125-128,共4页Chinese Journal of Contemporary Pediatrics

基　　金：广东省科技计划项目(No.2004B50301008);国家973项目(No.2001CB510305)。

摘　　要：c itrin缺陷导致的新生儿肝内胆汁淤积症(NICCD)是一种以黄疸、肝功能异常为主要临床表现的遗传代谢病。作为一种线粒体溶质载体蛋白,c itrin在糖有氧分解、糖异生、尿素循环以及蛋白质和核苷酸的合成过程中起重要作用,因此其缺陷可导致复杂多样的代谢紊乱,包括低血糖、高乳酸、高氨血症、低蛋白血症、高脂血症和半乳糖血症等。该文报道1例经SLC25A13(编码c itrin的基因)突变分析证实的NICCD病例。患儿为6个月男婴,因发现皮肤和巩膜黄染近半年入院,体查发现明显的皮肤和巩膜黄染,肝脏肋下5 cm,肝功能检查发现除GGT,ALP,AST,ALT等酶学指标升高外,TBA和Tb il(Db il为主)升高,而总蛋白/白蛋白和纤维蛋白原水平降低。血氨、血乳酸和血胆固醇、甘油三酯等指标也升高。AFP水平更是高达罕见的319 225.70μg/L。血串联质谱分析发现游离脂肪酸和酪氨酸、蛋氨酸、瓜氨酸和苏氨酸等氨基酸增高,尿UP-GC-MS分析检出大量的半乳糖和半乳糖醇。患儿于是被疑诊NICCD。停母乳喂养,予无乳糖和强化中链脂肪酸配方奶喂养,同时补充多种维生素(包括脂溶性的维生素A,D,E和K),并口服精氨酸降血氨治疗。经以上处理半月,患儿黄疸迅速消退,实验室指标改善或恢复正常。目前患儿已经门诊随访6月,体格生长发育正常,除有时有轻微的高乳酸血症外,实验室各项指标已经得以纠正。SLC25A13基因突变分析显示患儿系突变851del4和1638 ins23的复合杂合子。Neonatal intrahepatic cholestasis caused by citrin deficiency （NICCD） is a kind of inborn errors of metabolism, with the main clinic manifestations of jaundice, hepatomegaly, and abnormal liver function indices. As a mitochondrial solute carrier protein, citrin plays important roles in aerobic glycolysis, gluconeogenesis, urea cycle, and protein and nucleotide syntheses. Therefore citrin deficiency causes various and complicated metabolic disturbances, such as hypoglycemia, hyperlactic acidemia, hyperammonemia, hypoproteinemia, hyperlipidemia, and galactosemia. This paper reported a case of NICCD confirmed by mutation analysis of SLC25A13, the gene encoding citrin. The baby （ male, 6 months old） was referred to the First Affiliated Hospital with the complaint of jaundice of the skin and sclera, which it had suffered from for nearly 6 months. Physical examination showed obvious jaundice and a palpable liver 5cm below the right subcostal margin. Liver function tests revealed elevated enzymatic activities, like GGT, ALP, AST, and ALT, together with increased levels of TBA, bilirubin （ especially conjugated bilirubin ）, and decreased levels of total protein/albumin and fibrinogen. Blood levels of ammonia, lactate, cholesterol, and triglyceride were also increased, and in particular, the serum AFP level reached 319 225.70 μg/L, a extremely elevated value that has rarely been found in practice before. Tandem mass analysis of a dried blood sample revealed increased levels of free fatty acids and tyrosine, methionine, citrulline, and threonine as well. UP-GC-MS analysis of the urine sample showed elevated galactose and galactitol. The baby was thus diagnosed with suspected NICCD based on the findings. It was then treated with oral arginine and mutiple vitamins （including fat-soluble vitamins A, D, E, and K）, and was fed with lactose-free and medium-chain fatty acids enriched formula instead of breast feeding. After half a month of treatment, the jaundice disappeared, and the laboratory findings, includin

关 键 词：CITRIN citrin缺陷导致的新生儿肝内胆汁淤积症 甲胎蛋白 瓜氨酸 

分 类 号：R722.1[医药卫生—儿科]