Rod–Cone Dystrophy with Maculopathy in Genetic Glutathione Synthetase Deficiency: A Morphologic and Electrophysiologic Study

Abstract

To describe the retinal findings in 2 young adults with glutathione synthetase (GS) deficiency, an autosomal-recessive inborn error of glutathione (GSH) metabolism. Report of 2 cases. Binocular study in 2 affected siblings. Two sisters with severe GS deficiency underwent a first ophthalmologic examination including full-field electroretinogram (ERGs). The single flash and flicker ERGs and the oscillatory potentials were measured. The clinical examination was repeated after 1 year with the addition of fluorescein angiography, optical coherence tomography (OCT), and electrooculography (EOG). Angiograms and the retinal OCTs were analyzed, the morphologic findings compared, and the Arden ratio measured. Myopia decreased in both sisters, and visual acuity remained unchanged. Ophthalmoscopy showed bilateral retinal degenerative changes. Binocular cystic macular edema was present in the fovea and perifoveal areas. Cystic changes were located in the inner nuclear layer and outer plexiform layer. The ERGs showed low or no recordable rod-isolated b-waves, mixed rod-cone a- and b-waves, and cone responses. The oscillatory potentials were subnormal or nonrecordable. The EOG values were subnormal except in 1 eye of the older sister that had a normal Arden ratio. Severe GS deficiency is associated with progressive retinal dystrophy of the rod-cone type, affecting the central retina with advanced macular edema in adulthood. The retinal degenerative changes in GS deficiency may be the result of the increased oxidative stress accumulated generally in the retina and also apparent in the macular area, and an insufficient level of the free radical scavenger GSH. The patients with GS deficiency may represent a model of the retinal response to oxidative stress in humans. The authors have no proprietary or commercial interest in any materials discussed in this paper.