3例瓜氨酸血症Ⅰ型患儿基因与外周血代谢物表达特点  

Characteristics of Gene and Peripheral Blood Metabolite Expression in Three Children with Type 1 Citrullinemia

作　　者：武星宇 张春燕[2] 吴羽灵 蒋涛[2] 崔佳奕 程昱璇 舒杨 张民杰 桑培培 史文杰 檀旭东 田亚平[2] WU Xingyu;ZHANG Chunyan;WU Yuling;JIANG Tao;CUI Jiayi;CHENG Yuxuan;SHU Yang;ZHANG Minjie;SANG Peipei;SHI Wenjie;TAN Xudong;TIAN Yaping(Nankai University School of Medicine,Tianjin 300071,China;Birth Defects Prevention and Control Technology Research Center,Medical Innovation Research Department,General Hospital of the Chinese People’s Liberation Amy,Beijing 100853,China)

机构地区：[1]南开大学医学院,天津300071 [2]中国人民解放军总医院医学创新研究部出生缺陷防控技术研究中心,北京100853

出　　处：《标记免疫分析与临床》2022年第2期187-190,241,共5页Labeled Immunoassays and Clinical Medicine

基　　金：“科技助力经济2020”重点专项(编号:SQ2020YFF0426571)。

摘　　要：目的探究瓜氨酸血症I型患儿基因与外周血代谢物表达特点,提高临床对瓜氨酸血症I型的认识。方法收集瓜氨酸血症Ⅰ型患儿病例信息,利用液相串联质谱技术对3例瓜氨酸血症I型患儿进行外周血代谢物的测定,归纳总结瓜氨酸血症I型患儿外周血小分子代谢物表达特点,并且对瓜氨酸血症Ⅰ型患儿进行高通量二代测序,获取患儿的基因突变类型。结果3例患儿均出现了血氨和AST的增高,其他有患儿出现升高的生化指标包括AST、TBIL、DBIL以及GGT。且瓜氨酸水平均大幅增加,其他升高的氨基酸与氨基酸比值有蛋氨酸、精氨酸、蛋氨酸/苯丙氨酸以及瓜氨酸/苯丙氨酸,出现降低的包括甘氨酸、脯氨酸以及鸟氨酸/瓜氨酸,但是患儿的肉碱与酰基肉碱均没有异常。3例CTLN1患儿的ASS1基因均发生了变异,都为复合杂合突变,基因突变型分别为c.787G>A/c.1087C>T、c.794G>A/c.421-2A>G以及c.1168G>A/c.552C>A。结论CTLN1临床表现复杂多样,除了血氨以及瓜氨酸增高等典型症状外,也会出现明显的肝功能障碍以及其他氨基酸紊乱,但是不会发生肉碱以及酰基肉碱的异常。及时对瓜氨酸血症Ⅰ型患儿进行基因检测有助于明确诊断。Objective To explore the expression characteristics of gene and peripheral blood metabolites of type 1 citrullinemia,and to improve the clinical understanding of type 1 citrullinemia.Methods We collected clinical information of type 1 citrullinemia hematic disease cases of children and used tandem mass spectrometry for 3 cases to determine the peripheral blood metabolites,and summarized peripheral small molecule metabolites expression characteristics,and conducted second generation sequencing for gene mutations.Results Serum ammonia and AST were increased in all three cases,and other biochemical indicators including AST,TBIL,DBIL and GGT were also increased.The levels of citrulline increased significantly,and other amino acid to amino acid ratios increased,including methionine,arginine,methionine/phenylalanine and citrulline/phenylalanine,and ones decreased,including glycine,proline and ornithine/citrulline.However,carnitine and acylcarnitine were not abnormal in the children.ASS1 gene of the three children with citrullinemia type 1was mutated,all of which were complex heterozygous mutations,and the mutants were C.787g>A/C.1087C>T,C.794G>A/C.421-2A>G,and C.1168g>A/C.552c>A,respectively.Conclusion The clinical manifestations of type 1 citrullinemia are complex and varied.In addition to typical symptoms such as elevated serum ammonia and citrulline,type 1 citrullinemia also presents liver dysfunction and other amino acid disorders,but carnitine and acylcarnitine are not abnormal.Timely genetic testing of type 1 citrullinemia in children is helpful to confirm the diagnosis.

关 键 词：瓜氨酸血症Ⅰ型 液相色谱质谱联用 二代测序 氨基酸 ASS1基因 

分 类 号：R722.11[医药卫生—儿科]