Abstract：
Multiple mitochondrial dysfunction syndrome (MMDS) refers to a class of mitochondrial diseases caused by nuclear gene mutations, which usually begins in early infancy and is classically characterized by markedly impaired neurological development, generalized muscle weakness, lactic acidosis, and hyperglycinemia, cavitating leukoencephalopathy, respiratory failure, as well as early fatality resulted from dysfunction of energy metabolism in multiple systems. So far, six types of MMDS have been identified based on different genotypes, which are caused by mutations in NFU1, BOLA3, IBA57, ISCA2, ISCA1 and PMPCB, respectively. IBA57 encodes a protein involved in the mitochondrial Fe/S cluster assembly process, which plays a vital role in the activity of multiple mitochondrial enzymes. Herein, detailed clinical investigation of 2 Chinese patients from two unrelated families were described, both of them showed mildly delay in developmental milestone before disease onset, the initial symptoms were all presented with acute motor and mental retrogression, and brain MRI showed diffused leukoencephalopathy with cavities, dysplasia of corpus callosum and cerebral atrophy. Exome sequencing revealed three IBA57 variants, one shared variant (c.286T>C) has been previously reported, the remaining two (c.189delC and c.580 A>G) are novel. To enhance the understanding of this rare disease, we further made a literature review about the current progress in clinical, genetic and treatment of the disorder. Due to the rapid progress of MMDS, early awareness is crucial to prompt and proper administration, as well as genetic counseling.
摘要：
多发性线粒体功能障碍综合征(MMDS)是指由核基因突变引起的一类线粒体疾病,通常在婴儿期早期开始，其典型特征是神经发育明显受损，全身肌肉无力,乳酸性酸中毒,和高血糖症,空化性白质脑病,呼吸衰竭,以及早期死亡是由多个系统能量代谢功能障碍引起的。到目前为止,根据不同的基因型，已经鉴定出六种类型的MMDS，由NFU1，BOLA3，IBA57，ISCA2，ISCA1和PMPCB中的突变引起，分别。IBA57编码参与线粒体Fe/S簇组装过程的蛋白质，在多种线粒体酶的活性中起着至关重要的作用。在这里，描述了来自两个无关家庭的2名中国患者的详细临床调查，他们都在疾病发作前表现出轻微的发育里程碑延迟，最初的症状都表现为急性运动和精神倒退，脑MRI显示弥漫性白质脑病伴有空洞，胼胝体发育不良和脑萎缩。外显子组测序显示了三个IBA57变体，以前曾报道过一个共享变体(c.286T>C)，剩下的两个（c.189delC和c.580A>G）是新颖的。为了提高对这种罕见疾病的认识，我们进一步对目前的临床进展进行了文献综述，遗传和疾病的治疗。由于MMDS的快速发展，早期意识对于及时和适当的管理至关重要，以及遗传咨询。
