Mitochondrial maculopathy: geographic atrophy of the macula in the MELA aociated A to G 3243 mitochondrial DNA point mutation

PURPOE: To report ocular finding in the mitochondrial encephalomyopathy, lactic acidoi, and troke-like epiode (MELA yndrome) in a family with the A to G 3243 mitochondrial (mt) DNA point mutation. METHOD: Cae report. Ocular finding are decribed from four family member with the MELA aociated A to G 3243 mt DNA point mutation. REULT: Finding included ophthalmoplegia, neuroenory deafne, reduction of photopic and cotopic electroretinogram b-wave amplitude, and myopathy, a well a macular retinal pigment epithelial atrophy. No family member had nyctalopia, attenuation of retinal blood veel, or retinal bone picule pigmentation. CONCLUION: The finding of lowly progreive macular retinal pigment epithelial atrophy expand the reported phenotypic diverity of patient with A3243G mt DNA mutation. MELA yndrome (mitochondrial encephalomyopathy, lactic acidoi, and troke-like epiode) i a maternally inherited diorder aociated with abnormal mitochondria, manifeting in tiue highly dependent on oxidative metabolim. Ocular change in MELA yndrome have included reverible cotomata, ophthalmoplegia, pigmentary retinopathy, marked attenuation of the cotopic electroretinogram, myopia, and nuclear cataract.[1 and 2] We highlight ome of thee ocular manifetation in a family with MELA yndrome and decribe a ditinct maculopathy. A 48-year-old woman wa referred for evaluation of an aymptomatic maculopathy. Her medical hitory included mild enorineural hearing lo; her family hitory included a mother with congetive heart failure, diabete mellitu, ophthalmoplegia, and parafoveal atrophy a well a a deceaed brother who had an unknown ocular dieae, deafne, diabete, and heart failure. Ocular examination dicloed bet-corrected viual acuitie of RE: 20/25 and LE: 20/30, normal reult from Ihihara color plate teting, ignificant limitation of gaze in all field (a much a 70% of expected), and everal patche of macular retinal pigment epithelial atrophy bilaterally, which were noted to have become lightly larger compared with fundu photograph taken 8 year earlier. Thee region of atrophy correlated with cotomata on Amler grid and viual field teting (Figure 1 and Figure 2). Her electroretinogram dicloed reduction of photopic and cotopic b-wave amplitude with normal implicit time. creening for mitochondrial diorder wa uggeted but refued by the patient. Figure 1. Retinal pigment epithelial atrophy (arrow) of the right eye in a patient with heteroplamy for wild-type and A to G 3243 mt DNA mutation everal month later, the patient’ iter wa diagnoed with MELA yndrome after preenting with troke; he wa found to have bilateral neuroenory deafne, bicupid aortic valve, and diabete mellitu, and a mucle biopy wa poitive for ragged red mucle fiber. he wa noted to have ophthalmoplegia but did not have ophthalmic complaint. No family member had nyctalopia, waxy pallor of the optic nerve, or attenuation of the retinal veel. The four teted member of the family, including the iter with MELA yndrome a well a the original patient and her daughter and on, were found to have the A to G 3243 mt DNA mutation heteroplamic with wild-type mt DNA. Thi report amplifie and corroborate ome of the ophthalmic feature of MELA yndrome by decribing geographic atrophy of the macula in familie with the yndrome. The ymptom aociated with MELA yndrome typically appear in childhood and often caue death by the fourth decade.[3] Two mt DNA mutation have been aociated with thi yndrome and are both located in the tRNAleu (UUR) gene. In 80% of cae, the mutation i an A to G tranition at mt-3243, and in 10% of cae, the mutation i an A to G tranition at mt-3271. [4] Many maternal relative of patient with MELA yndrome exhibit a carcity of ymptom econdary to the preence of “heteroplamy,” a mixture of mutant and wild-type intracellular mitochondria. The mutant phenotype i expreed only when an intracellular threhold of mt DNA ha been reached. Mitochondrial mutation i uncommon in the general population; however, patient with the mutation were recently hown to have a wider range of phenotypic diverity than previouly reported. [5] Nutritional upplementation hould be conidered, although no large, well-deigned trial ha tudied it efficacy. [1] Atrophic macular pigment epithelial atrophy aociated with motility diorder and deafne hould precipitate an evaluation for mitochondrial diorder.