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Abstract：
To further comprehend the phenotype of multiple mitochondrial dysfunction syndrome type 3 (MMDS3:OMIM#615330) caused by IBA57 mutation. We present a case involving a patient who experienced acute neurological regression, and the literature was reviewed.
Clinical data and laboratory test results were collected; early language and development progress were tested; and genetic testing was performed. Bioinformatics analysis was performed using Mutation Taster and PolyPhen-2, and the literature in databases such as PubMed and CNKI was searched using MMDS3 and IBA57 as keywords.
The child, aged 1 year and 2 months, had motor decline, unable to sit alone, limited right arm movement, hypotonia, hyperreflexia of both knees, and Babinski sign positivity on the right side, accompanied by nystagmus. Blood lactate levels were elevated at 2.50 mmol/L. Brain MR indicated slight swelling in the bilateral frontoparietal and occipital white matter areas and the corpus callosum, with extensive abnormal signals on T1 and T2 images, along with the semioval center and occipital lobes bilaterally. The multiple abnormal signals in the brain suggested metabolic leukoencephalopathy. Whole-exome sequencing analysis revealed that the child had two heterozygous mutations in the IBA57 gene, c.286T>C (p.Y96H) (likely pathogenic, LP) and c.992T>A (p.L331Q) (variant of uncertain significance, VUS). As of March 2023, a literature search showed that 56 cases of MMDS3 caused by IBA57 mutation had been reported worldwide, with 35 cases reported in China. Among the 35 IBA57 mutations listed in the HGMD database, there were 28 missense or nonsense mutations, 2 splicing mutations, 2 small deletions, and 3 small insertions.
MMDS3 predominantly manifests in infancy, with primary symptoms including feeding difficulties, neurological functional regression, muscle weakness, with severe cases potentially leading to mortality. Diagnosis is supported by elevated lactate levels, multisystem impairment (including auditory and visual systems), and distinctive MRI findings. Whole-exome sequencing is crucial for diagnosis. Currently, cocktail therapy offers symptomatic relief.
Clinical data and laboratory test results were collected; early language and development progress were tested; and genetic testing was performed. Bioinformatics analysis was performed using Mutation Taster and PolyPhen-2, and the literature in databases such as PubMed and CNKI was searched using MMDS3 and IBA57 as keywords.
The child, aged 1 year and 2 months, had motor decline, unable to sit alone, limited right arm movement, hypotonia, hyperreflexia of both knees, and Babinski sign positivity on the right side, accompanied by nystagmus. Blood lactate levels were elevated at 2.50 mmol/L. Brain MR indicated slight swelling in the bilateral frontoparietal and occipital white matter areas and the corpus callosum, with extensive abnormal signals on T1 and T2 images, along with the semioval center and occipital lobes bilaterally. The multiple abnormal signals in the brain suggested metabolic leukoencephalopathy. Whole-exome sequencing analysis revealed that the child had two heterozygous mutations in the IBA57 gene, c.286T>C (p.Y96H) (likely pathogenic, LP) and c.992T>A (p.L331Q) (variant of uncertain significance, VUS). As of March 2023, a literature search showed that 56 cases of MMDS3 caused by IBA57 mutation had been reported worldwide, with 35 cases reported in China. Among the 35 IBA57 mutations listed in the HGMD database, there were 28 missense or nonsense mutations, 2 splicing mutations, 2 small deletions, and 3 small insertions.
MMDS3 predominantly manifests in infancy, with primary symptoms including feeding difficulties, neurological functional regression, muscle weakness, with severe cases potentially leading to mortality. Diagnosis is supported by elevated lactate levels, multisystem impairment (including auditory and visual systems), and distinctive MRI findings. Whole-exome sequencing is crucial for diagnosis. Currently, cocktail therapy offers symptomatic relief.
摘要：
目的：进一步了解IBA57突变引起的3型多发性线粒体功能障碍综合征（MMDS3：OMIM#615330）的表型。我们提出了一个病例，涉及一名经历急性神经消退的患者，并对文献进行了综述。
方法：收集临床数据和实验室检测结果；测试早期语言和发育进展；并进行基因检测。使用MutationTaster和PolyPhen-2进行生物信息学分析，并以MMDS3和IBA57为关键词检索PubMed和CNKI等数据库中的文献。
结果：孩子，1岁零2个月，有运动衰退，不能独自坐着，有限的右臂运动，低张力,双膝反射亢进,右边的巴宾斯基标志着积极，伴有眼球震颤.血液乳酸水平升高至2.50mmol/L。脑部MR提示双侧额顶叶和枕叶白质区域及call体轻度肿胀，T1和T2图像上有大量异常信号，以及两侧的半球形中心和枕叶。大脑中的多个异常信号提示代谢性白质脑病。全外显子组测序分析显示，该孩子在IBA57基因中有两个杂合突变，c.286T>C（p。Y96H)(可能致病，LP）和c.992T>A（p。L331Q)(意义不确定的变体，VUS）。截至2023年3月，文献检索显示，全球已报道56例由IBA57突变引起的MMDS3，在中国报告了35例。在HGMD数据库中列出的35个IBA57突变中，有28个错义或无义突变，2个剪接突变，2个小删除，和3个小插入。
结论：MMDS3主要表现在婴儿期，主要症状包括进食困难，神经功能退化,肌肉无力,严重病例可能导致死亡。乳酸水平升高支持诊断，多系统损害(包括听觉和视觉系统)，和独特的MRI发现。全外显子组测序对诊断至关重要。目前,鸡尾酒疗法可以缓解症状。
方法：收集临床数据和实验室检测结果；测试早期语言和发育进展；并进行基因检测。使用MutationTaster和PolyPhen-2进行生物信息学分析，并以MMDS3和IBA57为关键词检索PubMed和CNKI等数据库中的文献。
结果：孩子，1岁零2个月，有运动衰退，不能独自坐着，有限的右臂运动，低张力,双膝反射亢进,右边的巴宾斯基标志着积极，伴有眼球震颤.血液乳酸水平升高至2.50mmol/L。脑部MR提示双侧额顶叶和枕叶白质区域及call体轻度肿胀，T1和T2图像上有大量异常信号，以及两侧的半球形中心和枕叶。大脑中的多个异常信号提示代谢性白质脑病。全外显子组测序分析显示，该孩子在IBA57基因中有两个杂合突变，c.286T>C（p。Y96H)(可能致病，LP）和c.992T>A（p。L331Q)(意义不确定的变体，VUS）。截至2023年3月，文献检索显示，全球已报道56例由IBA57突变引起的MMDS3，在中国报告了35例。在HGMD数据库中列出的35个IBA57突变中，有28个错义或无义突变，2个剪接突变，2个小删除，和3个小插入。
结论：MMDS3主要表现在婴儿期，主要症状包括进食困难，神经功能退化,肌肉无力,严重病例可能导致死亡。乳酸水平升高支持诊断，多系统损害(包括听觉和视觉系统)，和独特的MRI发现。全外显子组测序对诊断至关重要。目前,鸡尾酒疗法可以缓解症状。
