case_images: PMC10729769_01
case_images: Interictal video-EEG recording at age 11 years: polygraphic recording during drowsiness showing a bilateral discharge of rhythmic sharply contoured delta waves (A); a similar activity but with right predominance (B) and right occipital spikes during sleep (circled area, C).
case_images: fneur-14-1284339-g001.jpg
case_images: PMC10729769_01_fneur-14-1284339-g001.jpg
case_images: fig1
case_images: CT and MRI scans were normal. Current, interictal video-EEG monitoring showed sporadic sharp waves in the occipital bilateral regions during sleep (Figure 1).
case_images: Clinical case history and evolution over time, including diagnostic procedures.
case_images: fneur-14-1284339-g002.jpg
case_images: PMC10729769_01_fneur-14-1284339-g002.jpg
case_images: fig2
case_images: The clinical history of the patient, evolution over time, and applied diagnostic procedures are summarized in Figure 2.
case_images: Structural analysis of AADC protein and localization of substituted amino acids. (A) AADC dimeric structure is represented as a cartoon. Chain A is blue and Chain B is cyan. PLP molecule for each active site is represented as red spheres. Leu391 and Arg347' in the heterodimeric protein are shown as yellow spheres. The prime indicates the residue and cofactor molecules belonging to subunit B. The active site where both variants may exert their effect is highlighted as a dashed circle. (B) Localization of Leu391. The cluster of hydrophobic residues (Phe77, Phe388, Phe448, and Trp464) shielded from the solvent is shown as blue sticks, while yellow sticks represent residues whose pathogenic substitutions lead to decreased affinity for the PLP molecule (red spheres). Protein visualization, measurement, dimer building, and rotamer analysis were performed using PyMOL 2.2.3, The PyMOL Molecular Graphics 50 System, Version 2.0 Schrodinger, LLC, New York, NY, 2021.
case_images: fneur-14-1284339-g003.jpg
case_images: PMC10729769_01_fneur-14-1284339-g003.jpg
case_images: fig3
case_images: In silico inspection of the AADC crystal structure shows that Leu391 is located on a surface alpha-helix of the C-terminal domain distant from the active site (Figure 3A), possibly involved in hydrophobic cluster stabilization important for folding and pyridoxal 5'-phosphate (PLP) binding (Figure 3B), since other pathogenic variants (Glu283Ala, Cys410Gly, Arg447His, Arg453Cys, and Arg462Gln) mapping in this protein region affect affinity for the coenzyme.