伴紫癜、抽搐和甲硫氨酸血症的citrin缺陷病患儿临床表型与基因突变分析  

Clinical investigation and mutation analysis of a child with citrin deficiency complicated with purpura, convulsive seizures and methioninemia

作　　者：温鹏强[1] 王国兵[1] 陈占玲[3] 刘晓红[2] 崔冬[1] 赏月[2] 李成荣[1] 

机构地区：[1]广东省深圳市儿童医院儿科研究所,518026 [2]广东省深圳市儿童医院新生儿科,518026 [3]东莞市人民医院内分泌科

出　　处：《中华医学遗传学杂志》2013年第6期649-653,共5页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金（81102227）;深圳市医学重点学科专项经费（2001818、2001819）;深圳市科技计划项目（医疗卫生类）重点项目（201201005）;广东省医学科研基金（A2012582）

摘　　要：目的分析1例伴紫癜、抽搐和甲硫氨酸血症为主要表现的citrin缺陷病患儿的临床特征，并探讨其SLC25A13基因突变类型。方法对患儿进行体格与一般实验室项目检查；应用串联质谱分析血氨基酸和肉碱浓度，气相色谱质谱法检测尿有机酸及半乳糖含量；应用高分辨率熔解曲线分析技术筛查SLC25A13基因18个外显子突变情况。结果患儿面部针尖样出血点和血小板计数减少（血小板计数：正常参考值为支持免疫性血小板减少性紫癜的诊断。常规实验室检查结果显示患儿凝血功能、心肌酶、肝功能、肝酶异常。串联质谱与气相色谱质谱结果提示患儿有甲硫氨酸血症（甲硫氨酸水平：正常参考值为但不表现有半乳糖血症、瓜氨酸血症和酪氨酸血症。SLC25A13基因突变分析发现患儿携带有IVSl6ins3kb突变，并且检测到第6外显子高分辨率熔解曲线异常，DNA测序证实患儿的SLC25A13基因第6外显子发生C．495delA突变，该突变在i00名正常对照中未检测到，为未报道过的新致病突变。家系突变分析显示患儿携带的c．495delA突变来源于父亲，IVS16ins3kb突变来源于母亲。结论citrin缺陷病具有临床异质性、生化代谢改变多样等特点。患儿临床症状的迁延不愈甚至有加重表现可能与C．495delA突变有关。Objective To analyze the clinical features and SLC25A13 gene mutations of a child with citrin deficiency complicated with purpura, convulsive seizures and methioninemia. Methods The patient was subjected to physical examination and routine laboratory tests. Blood amino acids and acylcarnitines, and urine organic acids and galactose were analyzed respectively with tandem mass spectrometry and gas chromatographic mass spectrometry. SLC25A13 gene mutation screening was conducted by high resolution melt （HRM） analysis. Results The petechiae on the patient＇ s face and platelet count （27 x 109/L, reference range 100 X 109/L 300 ）〈 109/L） supported the diagnosis of immunologic thrombocytopenic purpura （ITP）. Laboratory tests found that the patient have abnormal coagulation, cardiac enzyme, liver function and liver enzymes dysfunction. Tandem mass spectrometry also found methionine to be increased （286 bmol/L, reference ranges 8 p.mo[/I. 35 mol/L）. The patient did not manifest any galactosemia, citrullinemia and tyrosinemia. Analysis of SLC25A13 gene mutation found that the patient has carried IVS16ins3kb, in addition with abnormal HRM result for exon 6. Direct sequencing of exon 6 revealed a novel mutation e. 495delA. The same mutation was not detected in 100 unrelated healthy controls. Furtheranalysis of her family has confirmed that the c. 495delA mutation has derived from her farther, and that the IVS16ins3kb was derived from her mother. Conclusian The clinical features and metabolic spectrum of citrin deficiency can be variable. The poor prognosis and severity of clinical symptoms of the patient may be attributed to the novel c. 495delA mutation.

关 键 词：免疫性血小板减少性紫癜 抽搐 甲硫氨酸血症 CITRIN缺陷病 SLC25A13基因 高分辨率熔解曲线 遗传代谢病 

分 类 号：R725.9[医药卫生—儿科]