A Comparison of Phenotypic and Genotypic Features in Identical Twins with Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-like Episodes (MELAS) (P11-4.007)

Abstract

<h3>Objective:</h3> To discuss the presentation of MELAS in identical twins. <h3>Background:</h3> Mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) is characterized by normal early development, then poor growth, episodic lactic acidosis, seizures, and recurrent stroke-like episodes that can lead to an encephalopathy. It usually results from an adenine to guanine point mutation at position 3243 on the MT-TL1 (mitochondrially encoded tRNA leucine 1) gene. Identical twins with MELAS have been very rarely reported in the literature. The subjects in reported cases have had minimal differences in heteroplasmy. Our case report is unusual given unusual differences in heteroplasmy leading to different clinical courses. <h3>Design/Methods:</h3> Case report. <h3>Results:</h3> A pair of identical twins had apparent normal early development. However, by age 17, twin #1 developed an episode of bowel obstruction. Four years later, he had a first-time seizure with associated transient visual loss and genetic testing revealed the m.3243 A&gt;G mutation in MT-TL1, at 51% blood heteroplasmy. He subsequently had recurrent admissions for seizures, stroke-like episodes with visual and speech disturbances, and encephalopathy. He expired at age 26 during an exacerbation, due to septic shock. Twin #2 had a period of speech and memory disturbances requiring speech therapy at age 8. Four years later, he had the first of many recurrent bowel obstructions. At age 22, he developed seizures with bilateral transient visual loss. Genetic testing revealed the same mutation, but at 46% heteroplasmy. He subsequently had recurrent admissions with similar neurologic manifestations as his twin. <h3>Conclusions:</h3> The identical twins’ presentation is unusual as, to our knowledge, there have been no previously described MELAS cases with a comparable difference in heteroplasmy and clinical course. This adds to the literature on identical twins with MELAS and provides further insight into heteroplasmy and its implications in MELAS. <b>Disclosure:</b> Dr. Mbiziwo-Tiapo has nothing to disclose. Dr. Dugue has nothing to disclose. Dr. Libman has nothing to disclose.