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Brain MRI: a. Axial T2, showing global cerebral atrophy with ex-vacuo lateral ventricles dilatation; b. Sagittal T2, cerebellar atrophy; c. MR spectroscopy: the white asterisk (*) marks the lactate peak; d. axial T1 and e. susceptibility-weighted angiography (SWAN): mild bipallidal calcifications.
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The brain magnetic resonance imaging showed a global cerebral atrophy, cerebellar atrophy, white matter hyperintensities, bipallidal calcifications with a lactate peak on spectroscopy (Fig. 1). Sequencing of the whole muscular mtDNA, performed using Nextera XT technology (Illumina, San Diego, CA), showed the heteroplasmic (57%) m.3274_3275delAC MT-TL1 gene variant (Supplementary Figure 1).
Muscle biopsy reveals mild proliferation of mitochondria (a), COX negative fibers (b) and (c) one ragged blue fiber.
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Muscle biopsy revealed myopathic changes with scattered ragged red and blue fibers, as well as COX negative fibers (Fig. 2). Kidney biopsy (Supplementary Figure 2) demonstrated secondary focal segmental glomerulosclerosis associated to proximal tubulopathy: microscopy showed 7 glomeruli with global mesangial expansion and 2 of these with synecheal capsular adhesions with consensual parietal epithelial proliferation, which were not classifiable as tip lesion or vascular variants; mild focal tubular atrophy (5%) with associated mild fibrosis was also present.