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. 2026 Sep 29;20:1968308. doi: 10.3389/fnins.2026.1968308

Figure 2.

Multimodal characterization of the proband. Panel A shows brain MRI demonstrating prominence of cerebral and cerebellar sulci and a mega cisterna magna, together with thigh muscle MRI showing mild edema. Panel B shows muscle histology and electron microscopy demonstrating mitochondrial myopathic changes, ragged-red and ragged-blue fibers, lipid accumulation, and mitochondrial abnormalities. Panel C shows the blood acylcarnitine profile, with elevated species highlighted in red. Panel D compares fibroblast oxygen consumption between the patient and a healthy control. Panel E summarizes skeletal-muscle respiratory-chain enzyme activities, demonstrating isolated complex III deficiency.

Clinical, pathological, metabolic, and functional characterization of the proband. (A) Brain and muscle MRI at 12 years of age. (a,b) Brain MRI showing prominence of the cerebral and cerebellar sulci (arrows) and a mega cisterna magna (arrowhead). (c) Thigh muscle MRI demonstrating mild muscle edema. (B) Muscle pathology. (a) H&E staining showing variation in muscle fiber diameter and basophilic granular changes. (b) MGT staining showing ragged-red fibers (RRFs). (c) NADH-TR staining showing intense staining of RRFs. (d) SDH staining showing ragged-blue fibers (RBFs). (e) ORO staining showing lipid droplet accumulation. (f) PAS staining showing no abnormal glycogen accumulation. (g) COX-SDH staining showing preserved COX activity without COX-deficient fibers. (h) TEM showing mitochondrial accumulation and increased lipid droplets. Scale bars = 2 μm. (C) Acylcarnitine profile. Blood acylcarnitine profile showing elevated medium and long-chain acylcarnitines. C0, C2 and C3 are to be read on left scale while all other acylcarnitines are to be read on right scale. Black horizontal lines indicate the upper limits of the reference ranges, and elevated acylcarnitine species are highlighted in red. (D) Oxygen consumption rate (OCR). OCR profiles of patient-derived fibroblasts and healthy controls following sequential treatment with oligomycin, FCCP, and rotenone. (E) Mitochondrial respiratory chain (MRC) enzyme activities. MRC enzyme activities in skeletal muscle expressed as percentages of the normal control level, CS-normalized activities, and CoII-normalized activities, demonstrating an isolated CIII deficiency. Enzyme activities of CoI, CoII, and CS are expressed as nmol·min−1·mg protein−1; activities of CoIII and CoIV are expressed as first-order rate constants (nmol−1·min−1). H&E, hematoxylin and eosin; MGT, modified Gomori trichrome; NADH-TR, NADH-tetrazolium reductase; SDH, succinate dehydrogenase; ORO, Oil Red O; PAS, periodic acid–Schiff; COX, cytochrome c oxidase; TEM, transmission electron microscopy; OCR, oxygen consumption rate; FCCP, carbonyl cyanide phenylhydrazone.