School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, China.
Department of Pediatrics, Children's Hospital Affiliated to Shandong University, Jinan, Shandong, China.
Mol Genet Genomic Med. 2024 Jun;12(6):e2485. doi: 10.1002/mgg3.2485.
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.
进一步了解 IBA57 突变引起的多线粒体功能障碍综合征 3 型（MMDS3：OMIM#615330）的表型。我们报告了一例急性神经退行性疾病患者，并对文献进行了回顾。
收集临床资料和实验室检查结果，对早期语言和发育进展进行测试，进行基因检测。使用 Mutation Taster 和 PolyPhen-2 进行生物信息学分析，并使用 MMDS3 和 IBA57 作为关键词在 PubMed 和 CNKI 等数据库中搜索文献。
患儿 1 岁 2 个月，出现运动减退，独坐困难，右侧手臂活动受限，四肢无力，双膝关节反射亢进，右侧巴氏征阳性，伴眼球震颤。血乳酸水平升高至 2.50mmol/L。颅脑磁共振成像（MRI）显示双侧额顶枕及胼胝体脑白质区肿胀，T1、T2 加权像广泛异常信号，双侧半卵圆中心及枕叶受累。脑内多发异常信号提示代谢性脑白质病。全外显子组测序分析显示患儿 IBA57 基因存在 2 个杂合突变，c.286T>C（p.Y96H）（可能致病，LP）和 c.992T>A（p.L331Q）（意义不明的变异，VUS）。截至 2023 年 3 月，全球共报道 56 例 IBA57 突变引起的 MMDS3 病例，其中中国报道 35 例。HGMD 数据库中列出的 35 个 IBA57 突变中，有 28 个为错义或无义突变，2 个剪接突变，2 个小缺失，3 个小插入。
MMDS3 主要发生在婴儿期，主要症状包括喂养困难、神经功能进行性倒退、肌无力，严重者可导致死亡。诊断依据包括乳酸水平升高、多系统受累（包括听觉和视觉系统）和特征性 MRI 表现。全外显子组测序对诊断至关重要。目前，鸡尾酒疗法可缓解症状。
