Neuroimaging Characteristics and Genetic Correlations In Pediatric Mitochondrial Disorders: A Cohort Study From China

Background Mitochondrial disorders present with high clinical, genetic and neuroimaging variability. The spectrum of neuroimaging phenotype expanded fast based on the expanding of molecular etiologies. Methods In this study, we prospectively recruited a cohort of pediatric mitochondrial disorder patients with genetic diagnosis. The clinical presentation, neuroimaging data and genetic results were collected and reviewed. Results Seventy-seven patients were enrolled, including 54 patients with mtDNA (70.1%) and 23 patients with nDNA mutations (29.9%). The most common MRI findings were deep nuclei lesion (71.2%), brain atrophy (63.6%), cortical and subcortical white matter lesion (30.3%), deep white matter lesion (30.3%), and diffused cerebral atrophy (10.6%). Lesion in deep white matter, symmetrical deep nuclei lesion, and specific corpus callosum involvement was more common in nDNA-mutated patients (p=0.0365, p=0.0158 and p=0.0286). Deep nuclei lesion was observed most frequently in patients with mutations in MT-ATP6, MT-ND6, and NDUFAF5 genes, while cortical/subcortical white matter lesion was common in patients with MT-TL1 gene, mtDNA large-scale deletion, or NDUFAF5 gene defects. Stroke-like and deep nuclei lesion were often concurrent in patients with m.3243A>G mutation. Heatmap showed multi deep nuclei lesion was more common in patients with OXPHOS subunits defects; cortical and subcortical white matter lesion was more common in dysfunction of mtDNA maintenance, expression and translation; and lesion in deep white matter was more common in patients with dysfunction of metabolism of cofactors. Conclusion Neuroimaging features overlap in variable mitochondrial disorders. There is some correlation between neuroimage phenotype and genotype as well as biochemical defects.