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.