线粒体DNA耗竭是儿童期多种呼吸链缺陷的常见原因。

Mitochondrial DNA depletion is a prevalent cause of multiple respiratory chain deficiency in childhood.

作者信息

Sarzi Emmanuelle, Bourdon Alice, Chrétien Dominique, Zarhrate Mohamed, Corcos Johanna, Slama Abdelhamid, Cormier-Daire Valérie, de Lonlay Pascale, Munnich Arnold, Rötig Agnès

机构信息

INSERM U781, Hôpital Necker-Enfants Malades, Paris, France.

出版信息

J Pediatr. 2007 May;150(5):531-4, 534.e1-6. doi: 10.1016/j.jpeds.2007.01.044.

DOI:10.1016/j.jpeds.2007.01.044

PMID:17452231

Abstract

OBJECTIVE

To determine the actual incidence of mitochondrial DNA (mtDNA) depletion syndrome in multiple respiratory chain deficiency.

STUDY DESIGN

We carried out a real-time polymerase chain reaction quantification of mtDNA in liver or muscle tissue of 100 children with unexplained multiple oxidative phosphorylation enzyme deficiency.

RESULTS

A reduction of mtDNA copy number to <35% of control values was found in liver and/or muscle in half of the children (50/100). Most of these patients (32/50; 64%) presented with severe neonatal onset liver involvement; 7 (14%) had Alpers syndrome, and 11 (22%) exhibited various forms of neurologic involvement. Deoxyguanosine kinase or polymerase gamma (POLG) mutations could be identified in 11 of 32 patients with liver involvement, and POLG mutations were consistently found in all 7 patients with Alpers syndrome. Homozygous thymidine kinase 2 and MPV17 gene mutations were found in 2 patients.

CONCLUSIONS

Our findings show that mtDNA depletion is a prevalent cause of multiple respiratory chain deficiency in infancy.

摘要

目的

确定线粒体DNA（mtDNA）耗竭综合征在多重呼吸链缺陷中的实际发病率。

研究设计

我们对100例不明原因的多重氧化磷酸化酶缺乏症患儿的肝脏或肌肉组织进行了mtDNA的实时聚合酶链反应定量分析。

结果

半数患儿（50/100）的肝脏和/或肌肉中mtDNA拷贝数降至对照值的<35%。这些患者中大多数（32/50；64%）表现为严重的新生儿期肝脏受累；7例（14%）患有阿尔珀斯综合征，11例（22%）表现出各种形式的神经受累。在32例肝脏受累患者中有11例可鉴定出脱氧鸟苷激酶或聚合酶γ（POLG）突变，并且在所有7例阿尔珀斯综合征患者中均持续发现POLG突变。在2例患者中发现了纯合的胸苷激酶2和MPV17基因突变。