This implies that our patient's de novo somatic (and therefore uniformly vascular and glial because there is no reason to suspect mosaicism) mutation exerts secondary consequences on neurons (which are largely devoid of GLUT1). In the retina, Glut1-mediated transport occurs across capillary endothelial cells of the inner blood-retinal barrier and the retinal pigment epithelium (RPE). Together with the thickened choroid and decreased cone flicker, the simplest interpretation of our findings is early onset photoreceptor degeneration. The retinal changes were congruent across all imaging modalities: the retinal thinning noted on macular color thickness maps correlated with the hyperautofluorescence on FAF and with the area of reduced vessel density on OCTA. Our patient with G1D exhibited structural and functional retinal dysfunction. (A–F) See figure e-2 ( /NXG/A276) for comparison of all images to those of a normal subject. (G and H) OCT angiography (OCTA) of the superficial capillary plexus demonstrates decreased perimacular vessel density. Note that the fovea demonstrates subtle but abnormal hyperautofluorescence centrally this area normally shows hypoautofluorescence because of macular pigment AF blockage. (E and F) Wide-field fundus autofluorescence (FAF) images of the right and left eye, respectively, showing increased FAF in the perifoveal area corresponding to the area of retinal thinning depicted in (A and B). (C and D) OCT b-scans at the foveal centers demonstrate thickened retinal pigment epithelial layer interdigitation bands (red arrows) only at the foveal centers the bands disappear in the periphery of the scans.

(A and B) Optical coherence tomography (OCT) total macular color thicknessmaps (in microns) showing marked retinal thinning (blue-purple area) outside the fovea in the right and left eyes, respectively. OCT-angiography (OCTA) showed a paucity of perimacular vessels ( figure 1, G and H).įigure 1 Retinal multimodal imaging in a patient with GLUT1 deficiency Retinal fundus autofluorescence (FAF) demonstrated hyperautofluorescence outside the fovea and an unusual hyperautofluorescence in the central fovea ( figure 1, E and F). Swept source OCT demonstrated significant choroidal thickening (571 and 495 μm in the OD and OS, respectively normal for age: ∼330–400 μm). Optical coherence tomography (OCT) revealed retinal thinning in the posterior pole respecting the fovea ( figure 1, A and B) and absence of the interdigitation band peripherally with moderate photoreceptor layer thinning ( figure 1, C and D). Her visual acuity was 20/40 (OD) and 20/30 (OS) with no other obvious ocular abnormalities. 1, 4 The mutation introduced a dileucine motif in GLUT1 associated with clathrin recruitment and excessive internalization of cell membrane GLUT1. A 20-year-old woman with the common epileptic form of G1D reported subnormal visual acuity uncorrectable with glasses and harbored a de novo pathogenic SLC2A1 variant (c.1454C>T P485L).

Glut 1 2 3 4