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  • Grand Rounds

    A patient with diabetes and sensorineural deafness was referred to evaluate AMD in both eyes. She had been diagnosed with bilateral sensorineural hearing loss 10 years earlier. Genetic testing confirmed the m.3243A>G mutation in MT-TL1 gene, leading to a diagnosis of maternally inherited diabetes and deafness (MIDD). This rare mitochondrial disorder, caused by mitochondrial DNA (mtDNA) mutations, is characterized by progressive non-autoimmune diabetes and bilateral sensorineural hearing loss, typically manifesting in early adulthood. MIDD results from mitochondrial dysfunction, impairing aerobic metabolism and ATP synthesis. Consequently, tissues with high energy demands—including the nervous system, endocrine glands, heart, ears, eyes, and gastrointestinal tract—are frequently affected. Ocular manifestations include retinal pigmentary changes, progressive ophthalmoplegia, cataracts, and neuro-ophthalmologic abnormalities. The hallmark of mitochondrial retinopathy is pigmentary maculopathy that can progress to geographic atrophy. Type 1 and Type 2 disease are confined to the posterior pole, while Type 3 extends beyond the retinal vascular arcades, potentially progressing to chorioretinal atrophy. Ophthalmologists are sometimes the first to detect mitochondrial syndromes, making recognition of retinal findings crucial for early diagnosis. This presentation discusses the genetic basis, pathophysiology, clinical features, and management of MIDD, emphasizing its ophthalmic implications.

    Presentation Date: 02/06/2025
    Issue Date: 07/25/2025