PDF(Pubmed)
Abstract：
BACKGROUND: Mitochondrial diseases due to deficiencies in the mitochondrial oxidative phosphorylation system (OXPHOS) can be associated with nuclear genes involved in mitochondrial translation, causing heterogeneous early onset and often fatal phenotypes.
METHODS: The authors describe the clinical features and diagnostic workup of an infant who presented with an early onset severe encephalopathy, spastic-dystonic tetraparesis, failure to thrive, seizures and persistent lactic acidemia. Brain imaging revealed thinning of the corpus callosum and diffuse alteration of white matter signal. Genetic investigation confirmed two novel mutations in the GFM1 gene, encoding the mitochondrial translation elongation factor G1 (mtEFG1), resulting in combined deficiencies of OXPHOS.
CONCLUSIONS: The patient shares multiple clinical, laboratory and radiological similarities with the 11 reported patients with mutations involving this gene, but presents with a stable clinical course without metabolic decompensations, rather than a rapidly progressive fatal course. Defects in GFM1 gene confer high susceptibility to neurologic or hepatic dysfunction and this is, to the best of our knowledge, the first described patient who has survived beyond early childhood. Reporting of such cases is essential so as to delineate the key clinical and neuroradiological features of this disease and provide a more comprehensive view of its prognosis.
METHODS: The authors describe the clinical features and diagnostic workup of an infant who presented with an early onset severe encephalopathy, spastic-dystonic tetraparesis, failure to thrive, seizures and persistent lactic acidemia. Brain imaging revealed thinning of the corpus callosum and diffuse alteration of white matter signal. Genetic investigation confirmed two novel mutations in the GFM1 gene, encoding the mitochondrial translation elongation factor G1 (mtEFG1), resulting in combined deficiencies of OXPHOS.
CONCLUSIONS: The patient shares multiple clinical, laboratory and radiological similarities with the 11 reported patients with mutations involving this gene, but presents with a stable clinical course without metabolic decompensations, rather than a rapidly progressive fatal course. Defects in GFM1 gene confer high susceptibility to neurologic or hepatic dysfunction and this is, to the best of our knowledge, the first described patient who has survived beyond early childhood. Reporting of such cases is essential so as to delineate the key clinical and neuroradiological features of this disease and provide a more comprehensive view of its prognosis.
摘要：
背景：由于线粒体氧化磷酸化系统（OXPHOS）缺陷而引起的线粒体疾病可能与参与线粒体翻译的核基因有关，引起异质性的早期发作和通常致命的表型。
方法：作者描述了一个出现早发性严重脑病的婴儿的临床特征和诊断检查，痉挛型肌张力四轻瘫,未能茁壮成长，癫痫发作和持续性乳酸血症。脑成像显示call体变薄和白质信号的弥漫性改变。遗传调查证实了GFM1基因中的两个新突变，编码线粒体翻译延伸因子G1（mtEFG1），导致OXPHOS的综合缺陷。
结论：患者共有多个临床，与11例报道的涉及该基因突变的患者的实验室和放射学相似性，但表现出稳定的临床过程，没有代谢失代偿，而不是快速发展的致命过程。GFM1基因的缺陷赋予神经或肝功能障碍的高度易感性，据我们所知,第一个描述的病人存活到了童年早期。此类病例的报告对于描述该疾病的关键临床和神经放射学特征并提供其预后的更全面视图至关重要。
方法：作者描述了一个出现早发性严重脑病的婴儿的临床特征和诊断检查，痉挛型肌张力四轻瘫,未能茁壮成长，癫痫发作和持续性乳酸血症。脑成像显示call体变薄和白质信号的弥漫性改变。遗传调查证实了GFM1基因中的两个新突变，编码线粒体翻译延伸因子G1（mtEFG1），导致OXPHOS的综合缺陷。
结论：患者共有多个临床，与11例报道的涉及该基因突变的患者的实验室和放射学相似性，但表现出稳定的临床过程，没有代谢失代偿，而不是快速发展的致命过程。GFM1基因的缺陷赋予神经或肝功能障碍的高度易感性，据我们所知,第一个描述的病人存活到了童年早期。此类病例的报告对于描述该疾病的关键临床和神经放射学特征并提供其预后的更全面视图至关重要。
