case_images: PMC10764196_01
case_images: Brain MRI findings. At admission (18 days of life), axial diffusion-weighted imaging (DWI) and T1-weighted imaging, axial and sagittal T2-weighted images, along with left thalamic single voxel magnetic resonance spectroscopy (MRS) with echo time (TE) of 144 ms, do not reveal definite structural and metabolic brain abnormality. Three months later, axial DWI and corresponding apparent diffusion coefficient (ADC) maps show restricted diffusivity involving the cerebral peduncles, subthalamic nuclei (arrowheads), globi pallidi (thin arrows) and thalami (thick arrows). Additional linear lesions with restricted diffusivity are demonstrated in the deep white matter, abutting the caudate nuclei (open arrows). Axial and coronal T2-weighted images show increased signal in regions of restricted diffusivity. Single voxel MRS (TE 144 ms) of the left thalamic region shows a reduction of N-acetylaspartate (NAA) and a lactate doublet (see also Figure S1). At 5 months, DWI, T1- and T2-weighted images show reduced volume of the cerebral hemispheres, thalami, and basal ganglia (with cavitary lesion in both globi pallidi), no areas of restricted diffusivity, thinning of the posterior portion of the corpus callosum (open arrow) and ex-vacuo dilatation of the ventricular system and subarachnoid spaces, in keeping with atrophic changes. Left thalamic single voxel MRS (TE 144 ms) shows further reduction of NAA without evidence of lactate.
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case_images: The brain magnetic resonance imaging (MRI) performed at 18 months of age did not reveal any definite abnormalities (Figure 1). Localized magnetic resonance spectroscopy (MRS) of the left thalamic region demonstrated a reduction of N-acetylaspartate (NAA) and a lactate doublet (Figures 1 and S1). Localized MRS of the left thalamic region showed further reduction of NAA, without evidence of lactate (Figure 1).
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case_images: PMC10764196_06
case_images: Quantification of mitochondrial proteins in muscles' biopsies. Western blotting analysis and quantification expressed as a percentage (%) of (A) mitochondrial aconitase, (B) mitochondrial import receptor subunit (Tom20), and (C) mitochondrial Oxidative Phosphorylation System (OXPHOS) in muscles' biopsies (control and patient) are shown. Data were normalized on Vinculin amount in the same samples (Image Lab 4.0.1 Sofware, Bio-Rad, California, USA).
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case_images: The western blotting showed a significant reduction of mitochondrial aconitase protein levels of about 97% in the patient compared with the control subject (Figure 2A). Western blotting revealed a strong reduction of about 91% of the protein amount in the patient compared with the control subject (Figure 2B). TCA cycle is in direct relation with respiratory chain (OXPHOS) for the maintenance of balanced cellular metabolism, we evaluated the expression of the five complexes of the respiratory chain using the OXPHOS cocktail of antibodies on enriched mitochondrial proteins extracted from muscle biopsies. The results showed a statistically significant decrease in the expression of all the five complexes of the respiratory chain in the patient compared with the control (Figure 2C).