Abstract：
Multiple mitochondrial dysfunction syndrome type 3 (MMDS3) is a rare mitochondrial leukoencephalopathy caused by biallelic pathogenic variants in IBA57. Here, we describe a homozygous variant in IBA57, (NM_001010867.2): c.310G>T (p.Gly104Cys), in a 2-month-old infant of Cuban descent who presented with a one-month history of progressive hypotonia, weakness, and episodes of upgaze deviation. This is the first report of a patient homozygous for this variant and the first report of MMDS3 in a patient of Hispanic descent described to our knowledge. Using in silico tools, we found that the variant resides in a putative mutational hotspot located in the neighborhood of a key active ligand required for iron-sulfur cluster coordination. In addition, while previous case reports/series have reported the variable phenotypic features of the disease, the incidence of these features across the literature has not been well described. In order to construct a clearer global picture of the typical presentation of MMDS3, we reviewed 52 cases across the literature with respect to their clinical, biochemical, genotypic, and neuroradiographic features.
摘要：
3型多发性线粒体功能障碍综合征（MMDS3）是由IBA57的双等位基因致病变异引起的罕见线粒体白质脑病。这里,我们描述了IBA57中的纯合变体，（NM_001010867.2）：c.310G>T（p。Gly104Cys)，在一个2个月大的古巴裔婴儿中，他有一个月的进行性张力减退史，弱点,和向上凝视偏差的事件。这是该变体纯合患者的第一份报告，也是据我们所知，MMDS3在西班牙裔患者中的第一份报告。使用硅片工具，我们发现该变体位于假定的突变热点中，该热点位于铁硫簇配位所需的关键活性配体附近。此外,虽然以前的病例报告/系列报道了该疾病的可变表型特征，这些特征在整个文献中的发生率尚未得到很好的描述.为了构建更清晰的MMDS3典型表现的全局图景，我们回顾了52例文献中关于其临床，生物化学，基因型，和神经放射特征。
