Mitochondrial Infantile Liver Disease due to TRMU Gene Mutations: Three New Cases
Mitochondrial Infantile Liver Disease due to TRMU Gene Mutations: Three New Cases
复制标题
DOI：
10.1007/8904_2013_230
复制
发表时间：
2013-01-01
期刊：
影响因子：
--
通讯作者：
Slama, Abdelhamid
中科院分区：
文献类型：
--
作者：
Gaignard, Pauline;Gonzales, Emmanuel;Slama, Abdelhamid
合并呼吸链缺陷是婴儿期线粒体肝病的常见特征。由核基因Polg、DGUOK和MPV17突变引起的线粒体DNA枯竭是这些联合缺陷的主要原因。最近，在与线粒体翻译缺陷相关的婴儿肝病中发现了编码线粒体tRNA特异性2-硫代尿苷酸酶的TRMU基因突变。它的特征是呼吸链复合体的联合缺陷而没有线粒体DNA耗竭。我们报告了三名无血缘关系的儿童的临床、生化和遗传学结果，他们表现为肝病合并高乳酸血症和呼吸链缺陷，原因是TRMU基因的双等位基因突变。两名患者在几个月内自行康复，另一名患者死于急性肝功能衰竭。自发缓解是线粒体肝病的罕见特征，及早发现TRMU突变可能会对临床治疗产生影响。我们的结果扩展了在线粒体肝病中报道的少量TRMU突变，并允许积累基因-表型相关性的数据。
Combined respiratory chain defect is a common feature in mitochondrial liver disease during early infancy. Mitochondrial DNA depletions, induced by mutations of the nuclear genes POLG, DGUOK, and MPV17, are the major causes of these combined deficiencies. More recently, mutations in TRMU gene encoding the mitochondrial tRNA-specific 2-thiouridylase were found in infantile hepatopathy related to mitochondrial translation defect. It is characterized by a combined defect of respiratory chain complexes without mitochondrial DNA depletion.We report here clinical, biochemical, and genetic findings from three unrelated children presenting with hepatopathy associated with hyperlactatemia and respiratory chain defect due to bi-allelic mutations in TRMU gene. Two patients recovered spontaneously in a few months, whereas the other one died of acute liver failure. Spontaneous remission is a rare feature in mitochondrial liver diseases, and early identification of TRMU mutations could impact on clinical management. Our results extend the small number of TRMU mutations reported in mitochondrial liver disorders and allowed accumulating data for genotype-phenotype correlation.