A boy, aged 4 months, had the major clinical manifestations of prolonged jaundice and hepatomegaly. Multiple biochemical tests revealed abnormal liver function along with elevated alpha-fetoprotein and lactate. Genetic analysis confirmed that the boy had the mutations of c.589C>T(p.Gln197Ter) and c.687G>C(p.Trp229Cys) in the DGUOK gene, both of which were novel mutations and were determined to be pathogenic and likely pathogenic respectively, by a variety of bioinformatics tools and the ACMG standard. Therefore, the boy was confirmed to have DGUOK-related mitochondrial DNA depletion syndrome. Literature review showed that onset of liver disease in infancy was the main clinical feature of this disease, and some children presented with nervous system manifestations. Abnormal laboratory results included abnormal liver function, increases in blood lactate, serum ferritin and alpha-fetoprotein, and hypoglycemia. Such children had marked heterogeneity of DGUOK gene mutations, with missense mutations as the most common type. This disease tended to have a poor prognosis, and 79.6% of the children died before the age of 3 years.
该文患儿为4月龄男婴，主要临床表现为迁延性黄疸和肝脏肿大。多次生化检测结果均提示肝功能异常，伴甲胎蛋白和乳酸增高。遗传学分析结果证实患儿为DGUOK基因c.589C > T（p.Gln197Ter）和c.687G > C（p.Trp229Cys）突变，两者均为新突变类型，根据多种生物信息学软件及ACMG标准预测分别为致病性和可能致病性突变，从而确诊为DGUOK相关线粒体DNA耗竭综合征。文献复习发现，该病患儿以婴儿期起病的肝脏疾病表现为主要临床特征，部分患儿有神经系统表现。实验室检测结果主要表现为肝功能异常，血乳酸、血清铁蛋白和甲胎蛋白增高，以及低血糖。患儿DGUOK基因突变的异质性明显，其中错义突变最常见。该病预后不良，79.6%的患儿在3岁前死亡。