探讨DGUOK基因突变脑肝型线粒体DNA耗竭综合征(MDS)患儿的临床表现与诊治特点及产前诊断价值。

选择2018年1月，因"持续黄疸4个月＋19 d，肝功能异常1个月＋19 d"，于新疆维吾尔自治区人民医院确诊的1例脑肝型MDS患儿为研究对象。回顾性分析该例患儿的临床病例资料，包括临床诊治经过、基因突变特点等。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》。

①病史采集：患儿为女性，G₅P₃，入院年龄为4个月＋20 d，生后第2天出现黄疸并持续4个月＋19 d，伴眼球震颤及肝功能异常。其家族史中，曾有2例黄疸伴不明原因死亡新生儿。其4个月龄时罹患支气管肺炎、低蛋白血症并全身浮肿；5个月龄时，因呼吸、循环、肝等多脏器功能衰竭死亡。②基因检测结果：对该例患儿进行外周血线粒体核基因筛查结果显示，DGUOK基因第1外显子c.130G>A(p. Glu44Lys)纯合突变，为已知错义突变，并且为已报道的致病性突变。③产前诊断结果：该例患儿的母亲于30岁时再次妊娠。孕龄20孕周时，其羊水脱落细胞Sanger法测序结果显示，胎儿DGUOK基因第1外显子c.130G>A(p.Glu44Lys)杂合突变，被诊断为非MDS胎儿。

对于不明原因的肝病患儿，尤其累及多脏器或疑为酪氨酸血症时，应考虑MDS可能，通过基因分析可明确脑肝型MDS诊断。还可通过对胎儿羊水脱落细胞的基因分析，对MDS胎儿进行产前诊断。

To investigate clinical characteristics and prenatal diagnostic value of hepato-encephalopathy form of mitochondrial DNA depletion syndrome (MDS) caused by missense mutation variant in DGUOK gene.

A infant with hepato-encephalopathy form of MDS who was diagnosed and hospitalized in People′s Hospital of Xinjiang Uygur Autonomous Region in January 2018 due to " persistent jaundice for 4 months + 19 days and abnormal liver function for 1 months+ 19 days" , was selected as research subject. The clinical data of this case of infant were retrospectively analyzed, including clinical diagnosis and treatment process, gene mutation characteristics, etc..The procedure followed in this study was consistent with World Medical Association Declaration of Helsinki revised in 2013. For the treatment and genetic testing of the child, the informed consent of guardians was given and signed.

① Collection of medical history: this case of infant was a girl, G₅P₃, hospitalized in hospital at age of 4 months+ 20 days old. She developed jaundice on the second day after birth and lasted until 4 months+ 19 days old, accompanied with nystagmus and abnormal liver function. Her family history referred to 2 neonates with jaundice and unexplainable neonatal death. At the age of 4 months, this case of infant developed bronchopneumonia, hypoproteinemia and systemic edema. At the age of 5 months, she died of respiratory, circulatory, liver and other multiple organ failure. ②Genetic testing results: mitochondrial nuclear gene screening results of peripheral blood sample showed that she had homozygous mutation variant of exon 1: c. 130G>A (p. Glu44Lys) in DGUOK gene, which was known as missense mutation and a reported pathogenicity mutation variant. ③ Prenatal diagnosis results: mother of this case of hepato-encephalopathy form of MDS infant was pregnant again at 30 years old. Sanger sequencing of amniotic fluid cast off cells at 20 weeks of the pregnant woman showed exon 1: c. 130G>A (p.glu44lys) heterozygous mutation variant in DGUOK gene, and the fetus was free of MDS.

For children with unexplained liver disease, especially when multiple organs were involved or tyrosinemia was suspected, attention should be paid to the possibility of hepato-encephalopathy form of MDS, which can be clearly diagnosed through gene analysis. Prenatal diagnosis of fetus MDS could be made by gene analysis of amniotic fluid cast off cells of fetus.