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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 (NICCD) caused by citrin deficiency is a genetic metabolic disease characterized by jaundice and abnormal liver function. As a mitochondrial solute carrier protein, citrin plays an important role in the process of glycogenolysis, gluconeogenesis, urea cycle and the synthesis of proteins and nucleotides. Therefore, its defect can lead to complex and diverse metabolic disorders, including hypoglycemia , High lactic acid, hyperammonemia, hypoproteinemia, hyperlipidemia and galactosemia. This paper reports a case of NICCD confirmed by mutation analysis of SLC25A13 (gene encoding c-actin). Children with a 6-month-old boy, found yellowish scleral skin and sclera nearly six months after admission, physical examination found obvious skin and scleral yellow dye, the ribs 5 cm below the liver, liver function tests found that in addition to GGT, ALP, AST, ALT, etc. Enzyme markers increased, TBA and Tb il (Db il mainly) increased, while total protein / albumin and fibrinogen levels decreased. Blood ammonia, blood lactate and blood cholesterol, triglycerides and other indicators also increased. AFP levels are even as rare as 319 225.70 μg / L. Serum tandem mass spectrometry showed that amino acids such as free fatty acid, tyrosine, methionine, citrulline and threonine were increased, while urine and galactitol were detected by urine UP-GC-MS. Children were suspect NICCD. Breast-feeding is stopped, fed lactose-free and fortified medium-chain fatty acid formula supplemented with multivitamins (including fat-soluble vitamins A, D, E and K) and oral arginine heme treatment. After more than half of the treatment, jaundice in children quickly subsided, laboratory indicators to improve or return to normal. At present, children have been outpatient follow-up in June, physical growth and development of normal, except sometimes mild hyperlipidemia, the laboratory indicators have been corrected. SLC25A13 gene mutation analysis showed that the children were mutated 851del4 and 1638 ins23 complex heterozygotes.