Pigmentary retinal dystrophy and the syndrome of maternally inherited diabetes and deafness caused by the mitochondrial DNA 3243 tRNA(Leu) A to G mutation

Objective: To study the association of retinal disease and the syndrome of maternally inherited diabetes and deafness caused by an A to G mutation in the tRNA leucine gene at base pair 3243 (A3243G) of the mitochondrial genom e. Design: Observational study of a genetically defined subject group. Participants: Thirteen subjects with the mitochondrial DNA A3243G mutation from seven different pedigrees with maternally inherited diabetes and deafn ess. intervention: Assessment of visual symptoms and visual acuity, dilated indi rect ophthalmoscopy, retinal photography, and retinal electrophysiology, Main Outcome Measures: Loss of vision, funduscopic evidence of pigmentary r etinal disease or diabetic retinopathy, and electrophysiologic evidence of defective functioning of the retinal pigment epithelium/photoreceptor compl ex. Results: Funduscopic examination revealed abnormalities of retinal pigmenta tion in ten subjects (77%). Defects included speckled and patchy hyperpigme ntation at the posterior pole of the fundus, particularly in the macular ar ea, and varying degrees of loss of retinal pigmentation. Three subjects (23 %) had visual symptoms, which included night blindness, visual loss, and ph otophobia. Electrophysiologic studies revealed impaired electro-oculogram r esponses in four of nine subjects with defects of retinal pigmentation (44% ), two of whom also had much reduced scotopic and, to a lesser extent, flic ker electroretinogram b wave potentials. Two subjects had diabetic retinopa thy, including one with retinal depigmentation and impaired electro-oculogr am activity. Both subjects with diabetic retinopathy had unilateral reduced electroretinogram responses, especially oscillatory potentials. Conclusions: Abnormalities of retinal pigmentation are common in subjects w ith maternally inherited diabetes and deafness caused by the mitochondrial DNA A3243G mutation. Visual symptoms, in particular loss of visual acuity, appear to be infrequent. The combination of deficits in the electro-oculogr am and scotopic and flicker electroretinograms suggests that the retinal dy strophy includes defective functioning of retinal pigment epithelial cells and of both rod and cone photoreceptors. The pigmentary retinopathy does no t prevent diabetic retinopathy; a single subject had funduscopic and electr ophysiologic evidence of both diseases. Current evidence suggests that the mitochondrial DNA A3243G mutation accounts for 0.5% to 2.8% of diabetes. Mo st ophthalmic and diabetic clinics are therefore likely to contain such pat ients, who may benefit from identification of the genetic defect causing th eir disease and from genetic counseling.