G.P.189: Exercise intolerance associated with atypical facial muscle hypertrophy related to mitochondrial tRNA (Pro) gene mutation

Abstract

Exercise intolerance may be suggestive of metabolic myopathy or mitochondrial disorders. We report a family where 7 female subjects presented with various degree of exercise intolerance since childhood. A common and original feature shared by affected members was the increased volume of the masseter muscle systematically occurring after feeding, making them looking like a hamster. Limb muscle size was not affected by effort. Patients also complained of keloid scars and for some of them of congenital cataract. The index case underwent full examination including clinical assessment, electromyography, electro-retinography, muscle biopsy, pulmonary function testing, exercise test, genetic testing. Clinical and EDX examinations were normal. Exercise test was brief due to muscle fatigue but induced an important increase of lactates and lactate/pyruvate ratio. Morphological analysis and standard immunochemistry of the muscle biopsy were normal but analysis of the respiratory chain complexes from the muscle biopsy displayed a combined defect in the complexes I, III, and IV encoded by mitochondrial DNA, associated with an increase of complex II and citrate synthase. An increased number of muscle mtDNA copies was observed reflecting a probable mitochondrial proliferation. Whole mtDNA sequencing revealed the homoplasmic m.15992A > T variant in the mitochondrial tRNA (Pro) gene (MT-TP). This mutation does not affect the codon reading but modifies the efficiency of aminoacylation or of post-transcriptional modification, leading to less efficient translation. It was also found in 3 affected members apart from index case and is very likely to be pathological. The relationships between the gene mutation and the unusual clinical phenotype are not clear but are worthy of interest.