Mitochondrial Diabetes: The Clinical Spectrum of MIDD and MELAS in Association With the A3243G Mutation

Abstract Introduction: Maternally inherited diabetes and deafness (MIDD) is a multisystem disorder characterized by insulinopenia sensorineural hearing loss. This rare form of monogenic most commonly associated with the A3243G mutation mitochondrial DNA (mtDNA). The same seen in 80 percent patients MELAS (Mitochondrial encephalomyopathy lactic acidosis stroke-like episodes). MIDD have overlapping features suggesting continuum expression for mutation. Clinical Case: A 41-year-old male was referred genetic testing counseling his ophthalmologist following detection bilateral punched-out retinal pigment epithelium (RPE) lesions on routine exam. His medical history significant type 1 mellitus (T1DM) diagnosed at age 21 loss 38. referral triggered patient reported family two brothers who were both 10 died ages 20 27. Whether previously tested during early childhood remains unclear. negative episodes or seizures. Neurologic evaluation revealed mild fluent aphasia paraphasic errors some comprehension difficulties. MRI brain without contrast showed no focus restricted diffusion. Mitochondrial sequence analysis performed. pathogenic variant (m.3243 A>G) detected MT-TL1 gene approximately 25% heteroplasmy. advised to avoid metformin given increased risk acidosis. He also instructed against use statins. At 45, presented emergency department (ED) complaint headache, vertigo incoordination. Physical examination left homonymous hemianopsia, right horizontal nystagmus upper extremity dysmetria. large area predominantly cortical diffusion involving temporal occipital region T2/FLAIR hyper-intensity. Cross over between PCA MCA territories suggestive episode related MELAS. received bolus IV arginine 0.5 g/kg followed an infusion g/kg/day 3 days. later transitioned oral 5g three times daily discharged rehab facility. Lesson: case demonstrates evolution MELAS, supporting concept that syndromes represent spectrum disease. few reports describe progression Why develop others unclear but may be Early identification crucial comorbidities unique management issues.