case_images: PMC11422140_01
case_images: Cerebral magnetic resonance imaging and Proton spectroscopy at diagnosis. Diffusion-weighted imaging with Trace (A) and ADC map (B) shows restricted diffusion in the areas supposed to be myelinated [centrum semi-ovale (arrow), internal capsules and cortico-spinal tracts (*), optic radiations (#), dorsal brainstem (dotted arrow) and middle cerebellar peduncles (>)] consistent with intramyelinic edema, and vasogenic edemaof the frontal white matter (dotted arrow). Sagittal T2-weighted image (C) shows normal corpus callosum. Axial T1-weighted image (D) shows attenuated signal of the expected myelinated internal capsules (arrow). Proton spectroscopy (E) with intermediate echo time (144 ms) shows glycine peak (arrow; note that myo-inositol has a similar chemical shift but is not expected at 144 ms because of short T2 relaxation time) and lactate inverted doublet peaks (dotted arrow).
case_images: fgene-15-1432272-g002.jpg
case_images: PMC11422140_01_fgene-15-1432272-g002.jpg
case_images: F2
case_images: Proton spectroscopy revealed glycine and lactate peaks, initially suggestive of NKH (Figure 2).
case_images: PMC11422140_02
case_images: PMC11422140_03
case_images: PMC11422140_04
case_images: (A) Genetic Variations in the GLRX5 Gene Associated with Sideroblastic Anemia (red) and Hyperglycinemia (blue). p.Asp123His described in this case is higlighted (yellow). Functional domains prediction from Uniprot.org
  (B) Visualization of the Interaction Site in GLRX5 Tetramer. Global view and focused view of the interaction site at position 123 (cyan) in a GLRX5 monomer (green). The second GLRX5 monomer is shown in pink. Glutathione are represented in deep blue. Fe-2S bridges are indicated in orange and yellow and oxygens are depicted in red. Variation Asp123His is predicted to result in the lost of several hydrogen bonds and provoke steric clash between His123 and Pro107(*) + Thr108 (**) of the interacting monomer [prediction via https://miztli.biokerden.eu/and ]. The structure is visualized using the PDB file 2WUL on the rcsb.org website.
case_images: fgene-15-1432272-g003.jpg
case_images: PMC11422140_04_fgene-15-1432272-g003.jpg
case_images: F3
case_images: This analysis led to the identification of a homozygous variation, c.367G>C; p. (Asp123His), located on exon 2 of the GLRX5 gene (NM_016417.3) (Figure 3A). The variant is situated within the critical Glutaredoxin protein domain (PM1 criteria) as depicted in Figure 3B, who shows that this protein is a tetramer constituted by 4 GLRX5 monomers.
case_images: PMC11422140_05