线粒体MT-TE基因突变致可逆性婴幼儿呼吸链缺乏症1例并文献复习
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摘要
目的探讨线粒体MT-TE基因突变致可逆性婴幼儿呼吸链缺乏症的临床表现及基因突变特点。方法回顾分析1例确诊为可逆性婴幼儿呼吸链缺乏症患儿的临床资料,并复习相关文献。结果男性患儿,2个月23天,入院时消瘦,呼吸急促,双肺可闻及痰鸣音及喘鸣音;肌力IV级,肌张力减弱。有一胞姐生后不久因重症肺炎去世。入院时肌酸激酶同工酶123 U/L,肌酸激酶890 U/L;血乳酸8.9 mmol/L;病原学检查均为阴性。头颅MRI无异常。入院后患儿持续高乳酸血症、肌酶异常升高,伴呼吸困难,放弃治疗后死亡。基因检查示线粒体MT-TE基因存在14674T>C突变,来源于母亲。国外文献报道线粒体MT-TE 14674T>C突变患儿早期临床表现与进展型线粒体病类似,呼吸肌无力、喂养困难,运动发育里程碑延迟,肌酶及乳酸升高。予补充能量,维持内环境稳定等治疗,约1岁左右逐渐好转。结论线粒体MT-TE基因突变致可逆性婴幼儿呼吸链缺乏症早期表现与进展型线粒体病类似,积极治疗预后良好。早期进行基因检测可明确预后,增强治疗的信心。
Objective To investigate the characteristics of clinical manifestation and gene mutation of reversible respiratory chain deficiency in infants with mitochondrial MT-TE gene mutation. Methods Clinical data of a child diagnosed as reversible infantile respiratory chain deficiency was retrospectively analyzed and related literature was reviewed. Results A male infant, 2 months and 23 days, presented with low weight, short of breath, both lungs can hear snoring and wheezing, hypotonia,and level IV muscle strength. One of his sisters died of severe pneumonia shortly after birth. At the time of admission, blood test showed creatine kinase isoenzyme 123 U/L, creatine kinase 890 U/L, blood lactate 8. 9 mmol/L, and pathogen examination were negative. There was no abnormality in the head MRI. After admission, the child continued to have high lactatemia, abnormal muscle enzymes, and difficult breath, and died after giving up treatment. Genetic testing revealed a 14674 T>C mutation in the mitochondrial MT-TE gene, which was inherited from his mother. Literature reports found that early clinical manifestations of patients with mitochondrial MT-TE 14674 T>C mutations are similar to progressive mitochondrial diseases which is characterized by respiratory muscle weakness, feeding difficulties, delayed motor development milestones, increased muscle enzymes and lactic acid. Replenish energy, maintain internal stability and other treatments could gradually improve clinical symptom around1 year old. Conclusions This case is a reversible infantile respiratory chain deficiency caused by a mitochondrial MT-TE mutation. Early manifestations of this disease are similar to those of progressive mitochondrial disease, and the prognosis is good.Early genetic testing can confirm the prognosis and enhance the confidence of treatment.
Objective To investigate the characteristics of clinical manifestation and gene mutation of reversible respiratory chain deficiency in infants with mitochondrial MT-TE gene mutation. Methods Clinical data of a child diagnosed as reversible infantile respiratory chain deficiency was retrospectively analyzed and related literature was reviewed. Results A male infant, 2 months and 23 days, presented with low weight, short of breath, both lungs can hear snoring and wheezing, hypotonia,and level IV muscle strength. One of his sisters died of severe pneumonia shortly after birth. At the time of admission, blood test showed creatine kinase isoenzyme 123 U/L, creatine kinase 890 U/L, blood lactate 8. 9 mmol/L, and pathogen examination were negative. There was no abnormality in the head MRI. After admission, the child continued to have high lactatemia, abnormal muscle enzymes, and difficult breath, and died after giving up treatment. Genetic testing revealed a 14674 T>C mutation in the mitochondrial MT-TE gene, which was inherited from his mother. Literature reports found that early clinical manifestations of patients with mitochondrial MT-TE 14674 T>C mutations are similar to progressive mitochondrial diseases which is characterized by respiratory muscle weakness, feeding difficulties, delayed motor development milestones, increased muscle enzymes and lactic acid. Replenish energy, maintain internal stability and other treatments could gradually improve clinical symptom around1 year old. Conclusions This case is a reversible infantile respiratory chain deficiency caused by a mitochondrial MT-TE mutation. Early manifestations of this disease are similar to those of progressive mitochondrial disease, and the prognosis is good.Early genetic testing can confirm the prognosis and enhance the confidence of treatment.
引文
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[2]Schapira AH.Mitochondrial diseases[J].Lancet,2012,379(9828):1825-1834.
[3]Mimaki M,Hatakeyama H,Komaki H,et al.Reversible infantile respiratory chain deficiency:a clinical and molecular study[J].Ann Neurol,2010,68(6):845-854.
[4]韩晓蕾,李永昶.细胞色素C氧化酶缺乏的可逆性线粒体肌病[J].国外医学儿科学分册,1993,20(3):99.
[5]Ulrike S,Adela DM,Rita H.Rever sible infantile respiratory chain deficiency.Chapter 15,Mitochondrial case studies underlying mechanisms and diagnosis[M].Elsevier,2016,127-133.
[6]Paim J,Cotta A,Navarro M,et al.Clinical,muscle biopsy and image findings in reversible infantile respiratory chain deficiency,[J]Neuromuscul Disord,2016,26:S175-S176.
[7]Boczonadi V,Bansagi B,Horvath R.Reversible infantile mitochondrial diseases[J].J Inherit Metab Dis,2015,38(3):427-435.
[8]DiMauro S,Nicholson JF,Hays AP,et al.Benign infantile mitochondrial myopathy due to reversible cytochrome c oxidase deficiency[J].Trans Am Neurol Assoc,1981,106:205-207.
[9]Horvath R,Kemp JP,Tuppen HA,et al.Molecular basis of infantile reversible cytochrome c oxidase deficiency myopathy[J].Brain,2009,132(Pt11):3165-3174.
[10]Uusimaa J,Jungbluth H,Fratter C,et al.Reversible infantile respiratory chain deficiency is a unique,genetically heterogenous mitochondrial disease[J].J Med Genet,2011,48(10):660-668.
[11]Yang L,Long Q,Liu J,et al.Mitochondrial fusion provides an‘initial metabolic complementation'controlled by mtDNA[J].Cell Mol Life Sci,2015,72(13):2585-2598.
[12]Salo MK,Rapola J,Somer H,et al.Reversible mitochondrial myopathy with cytochrome C oxidase deficiency[J].Arch Dis Child,1992,67(8):1033-1035.