婴儿脑肌病型线粒体DNA耗竭综合征1例报告

发布时间：2018-03-17 04:33

本文选题：线粒体病　切入点：线粒体DNA耗竭综合征　出处：《临床儿科杂志》2017年11期 　论文类型：期刊论文

【摘要】：目的分析罕见的常染色体隐性遗传病——线粒体DNA耗竭综合征的临床及基因突变特点。方法回顾分析1例线粒体DNA耗竭综合征患儿的临床及基因检测资料。结果患儿,男,生后4个月出现肢体无力,9个月就诊时呈营养不良貌,发育落后,四肢肌力、肌张力低下,伴脊柱侧弯、后凸。血清乳酸、丙酮酸增高,肝功能、心肌酶谱异常;血液多种氨基酸降低,丁二酰肉碱增高;尿甲基丙二酸及其代谢产物浓度轻度增高,提示甲基丙二酸尿症。头颅MRI显示双侧豆状核及尾状核萎缩,伴长T2信号及脑萎缩样改变。脑干听觉诱发电位示重度感音神经性耳聋。严重发育落后。基因测序示MUT、MMAA、MMAB等甲基丙二酸尿症相关基因未见可疑致病突变;SUCLG1基因存在c.961CG(p.A321P)与c.713 TC(p.D 238 G)两个杂合突变,分别来自表型正常的父母,其中c.961 CG为已知致病突变,c.713 TC为未报道新突变。外周血白细胞线粒体DNA拷贝数降低,为244/cell,为正常对照的68.4%。确诊线粒体DNA耗竭综合征。结论不明原因发育落后、肌张力低下、听力障碍伴高乳酸血症、轻度甲基丙二酸血症患儿应考虑线粒体DNA耗竭综合征可能,基因分析可明确诊断。
[Abstract]:Objective to analyze the clinical and gene mutation characteristics of mitochondrial DNA depletion syndrome, a rare autosomal recessive disease. Methods A case of mitochondrial DNA depletion syndrome was retrospectively analyzed. Limb weakness appeared at 4 months after birth, dystrophy appeared at 9 months, dystrophy, hypotony, scoliosis and kyphosis. Serum lactic acid, pyruvate increased, liver function abnormal and myocardial enzyme spectrum abnormal. The decrease of blood amino acids and the increase of succinylcarnitine, the slight increase in the concentration of urinary methylmalonic acid and its metabolites suggest that the MRI of the head shows atrophy of bilateral lentiform and caudate nuclei. Brain-stem auditory evoked potential (BAEP) showed severe sensorineural deafness and severe developmental retardation. Gene sequencing showed no suspicious mutation of SUCLG1 gene in MMAAMAMMAB and other methylmalonuria related genes. C. 961CGP p.A321P) and c.713 TC(p.D 238G), Among the parents with normal phenotype, c. 961 CG was a known pathogenic mutation and c. 713 TC was a new mutation. The mitochondrial DNA copy number of peripheral white blood cells was decreased. The diagnosis of mitochondrial DNA depletion syndrome was confirmed as 24.4% cell, 68.4% of normal control. Conclusion the mitochondrial DNA depletion syndrome should be considered in children with unexplained developmental retardation, hypotonia, hearing disorder and hyperlactic acidemia, and mild methylmalonic acidemia, and the possibility of mitochondrial DNA depletion syndrome should be taken into account in children with mild methylmalonic acidemia. Gene analysis can make a definite diagnosis.
【作者单位】：河南中医药大学第一附属医院儿科;北京大学第一医院;北京福佑龙惠遗传专科门诊部;
【基金】：十二五国家科技支撑计划课题(No.2012BAl09804) 国家自然科学基金项目(No.81471097)
【分类号】：R725.9

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