CAJ | 학술논문

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.:27×109/L,正常参考值为100×109/L～300×109/L)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:286 μmol/L;正常参考值为8 μmol/L～35 μmol/L),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IVS16ins3kb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100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.
목적 분석1례반자전、추휵화갑류안산혈증위주요표현적citrin결함병환인적림상특정,병탐토기SLC25A13기인돌변류형.방법 대환인진행체격여일반실험실항목검사;응용천련질보분석혈안기산화육감농도,기상색보질보법검측뇨유궤산급반유당함량;응용고분변솔용해곡선분석기술사사SLC25A13기인18개외현자돌변정황.결과 환인면부침첨양출혈점화혈소판계수감소(혈소판계수.:27×109/L,정상삼고치위100×109/L～300×109/L)지지면역성혈소판감소성자전적진단.상규실험실검사결과현시환인응혈공능、심기매、간공능、간매이상.천련질보여기상색보질보결과제시환인유갑류안산혈증(갑류안산수평:286 μmol/L;정상삼고치위8 μmol/L～35 μmol/L),단불표현유반유당혈증、과안산혈증화락안산혈증.SLC25A13기인돌변분석발현환인휴대유IVS16ins3kb돌변,병차검측도제6외현자고분변솔용해곡선이상,DNA측서증실환인적SLC25A13기인제6외현자발생c.495delA돌변,해돌변재100명정상대조중미검측도,위미보도과적신치병돌변.가계돌변분석현시환인휴대적c.495delA돌변래원우부친,IVS16ins3kb돌변래원우모친.결론 citrin결함병구유림상이질성、생화대사개변다양등특점.환인림상증상적천연불유심지유가중표현가능여c.495delA돌변유관.
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 × 109/L,reference range 100 × 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 μmol/L,reference ranges 8 μmol/L 35 μmol/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 c.495delA.The same mutation was not detected in 100 unrelated healthy controls.Further analysis of her family has confirmed that the c.495delA mutation has derived from her farther,and that the IVS16ins3kb was derived from her mother.Conclusion 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.