Intramyocellular lipid excess in the mitochondrial disorder MELAS

OBJECTIVE There is a paucity of objective, quantifiable indicators of mitochondrial disease available for clinical and scientific investigation. METHODS To this end, we explore intramyocellular lipid (IMCL) accumulation noninvasively by 7T magnetic resonance spectroscopy (MRS) as a reporter of metabolic dysfunction in MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes). We reasoned that mitochondrial dysfunction may impair muscle fat metabolism, resulting in lipid deposition (as is sometimes observed in biopsies), and that MRS is well suited to quantify these lipids. RESULTS In 10 MELAS participants and relatives, IMCL abundance correlates with percent mitochondrial DNA mutation abundance and with disease severity. CONCLUSIONS These results indicate that IMCL accumulation is a novel potential disease hallmark in MELAS.