A-143 Understanding the Heterogeneous Effects of MELAS: A Comparative Study of Juvenile Sisters

Abstract Objective: Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a rare syndrome resulting from mutations in mitochondrial DNA. A neuropsychological profile of MELAS typically shows deficits in executive function, attention, language, memory, visuospatial, and motor functioning. To our knowledge, MELAS has been studied in single cases only. Here we examine the neuropsychological profile of juvenile siblings with MELAS. Participants and Methods: Biological sisters aged 13 (affected) and 11 (non-affected) years, concordant for MELAS mutation but discordant for disease status. Active disease in the affected sister was triggered by HGH treatment for small stature. They were referred for neuropsychological testing to determine the nature and severity of current cognitive, emotional, and functional deficits following MELAS diagnoses. Clinical difference in cognitive performance score was defined as a difference of >1 SD in standardized scores. Results: Performance on 48 neuropsychological test measures consistent with the MELAS presentation were contrasted between the sisters. The unaffected sister performed in the average range on most measures. The affected sister performed >1 standard deviation lower on 21 measures compared to the unaffected sister -- specifically on measures of motor strength, motor speed, visuomotor integration, visuospatial abilities, executive functioning, broad math, academic applications, phonological awareness, and rapid symbolic naming. Conclusions: The results of this study reveal differences in the cognitive profiles of juvenile siblings with the MELAS mutation but different disease status (affected vs. not affected). Results are generally consistent with previous research in revealing deficits in executive functioning, visuospatial abilities, motor functioning, and language in the affected sibling.