Zhao M X, Wang J S, Gong J Y
Department of Pediatrics, Jinshan Hospital of Fudan University, Shanghai 201508, China.
Department of Infectious Disease, Children's Hospital of Fudan University, Shanghai 201102, China.
Zhonghua Er Ke Za Zhi. 2022 May 2;60(5):457-461. doi: 10.3760/cma.j.cn112140-20210827-00711.
To explore the clinical features of hepatocerebral mitochondrial DNA depletion syndrome (MDS). The clinical data of 6 hepatocerebral MDS patients diagnosed in the Jinshan Hospital of Fudan University from January 2012 to December 2019 were retrospectively collected and analyzed. Related literature published before January 2020 were searched with the key words of "DGUOK""MPV17""POLG""C10orf2" in PubMed, China national knowledge infrastructure (CNKI) and Wanfang database. All the 6 hepatocerebral MDS cases were male. The age of onset ranged from 3 days to 8 months. The most common initial symptoms were cholestasis and developmental retrogression. The main clinical manifestations included hepatomegaly (4 cases), hypotonia (3 cases), growth retardation (4 cases), cholestasis (5 cases), coagulopathy (5 cases), hypoalbuminemia (3 cases), hypoglycemia (4 cases), hyperlactacidemia (5 cases), and abnormal blood metabolism screening (6 cases). The isotope hepatobiliary imaging revealed no gallbladder and intestinal tract development within 24 hours in 2 patients. Regarding the cranial imaging examination, the head CT found widening of the extracranial space in 1 case, the brain magnetic resonance imaging (MRI) found ventricular enlargement in 2 cases, and the brain ultrasound found peripheral white matter injury in 1 case. Two cases were lost to follow-up, one died of liver failure, and three died of multiple organ failure due to aggravated infection. Among the 6 cases, there were 3 with MPV17 variation (c.182T>C and c.279G>C were novel), 1 with POLG variation (c.2993G>A was novel), 1 with DGUOK variation (c.679G>A homozygous mutation, parthenogenetic diploid of chromosome 2) and 1 with C10orf2 variation (c.1186C>T and c.1504C>T were novel). The literature review found that 129, 100, 51 and 12 cases of hepatocerebral MDS were caused by DGUOK, MPV17, POLG and C10orf2 gene variations, respectively. And the most common clinical manifestations were liver dysfunction presented with cholestasis and elevated transaminase, metabolic disorders including hypoglycemia and hyperlactacidemia, and diverse neurologic symptoms including developmental retardation, hypotonia, epilepsy and peripheral neuropathy. Besides, 1/3 of the patients with C10orf2 variation developed renal tubular injury. Hepatocerebral MDS mainly present with liver dysfunction, metabolic disorder and neuromuscular impairment. Different genotypes show specific clinical manifestations.
探讨肝脑型线粒体DNA耗竭综合征（MDS）的临床特征。回顾性收集并分析2012年1月至2019年12月在复旦大学附属金山医院确诊的6例肝脑型MDS患者的临床资料。以“DGUOK”“MPV17”“POLG”“C10orf2”为关键词，检索2020年1月以前在PubMed、中国知网（CNKI）和万方数据库发表的相关文献。6例肝脑型MDS患者均为男性。发病年龄为3天至8个月。最常见的首发症状为胆汁淤积和发育倒退。主要临床表现包括肝肿大（4例）、肌张力低下（3例）、生长发育迟缓（4例）、胆汁淤积（5例）、凝血功能障碍（5例）、低白蛋白血症（3例）、低血糖（4例）、高乳酸血症（5例）及血液代谢筛查异常（6例）。同位素肝胆显像显示2例患者24小时内胆囊及肠道未显影。头颅影像学检查方面，头颅CT发现1例颅外间隙增宽，脑磁共振成像（MRI）发现2例脑室扩大，脑超声发现1例脑白质外周损伤。2例失访，1例死于肝功能衰竭，3例因感染加重死于多器官功能衰竭。6例患者中，3例存在MPV17变异（c.182T>C和c.279G>C为新变异），1例存在POLG变异（c.2993G>A为新变异），1例存在DGUOK变异（c.679G>A纯合突变，2号染色体单亲二倍体），1例存在C10orf2变异（c.1186C>T和c.1504C>T为新变异）。文献复习发现，分别有129、100、51和12例肝脑型MDS由DGUOK、MPV17、POLG和C10orf2基因变异引起。最常见的临床表现为以胆汁淤积和转氨酶升高为表现的肝功能障碍、包括低血糖和高乳酸血症在内的代谢紊乱以及包括发育迟缓、肌张力低下、癫痫和周围神经病变在内的多种神经症状。此外，1/3的C10orf2变异患者发生肾小管损伤。肝脑型MDS主要表现为肝功能障碍、代谢紊乱和神经肌肉损害。不同基因型表现出特定的临床表现。
