Nonsense mutations in mitochondrial DNA associated with myalgia and exercise intolerance

Exercise intolerance 1 We describe a patient with young-onset severe exercise intolerance initially believed to have chronic fatigue. We identified a novel heteroplasmic nonsense mutation in the mtDNA ND2 gene. We suggest mitochondrial investigations should be considered in certain patients with chronic fatigue, especially those with young onset. A 49-year-old woman had experienced exercise intolerance since the first decade of her life. She was unable to engage in sports at school and always had great difficulty with repetitive motor tasks of daily life because of fatigue and myalgia. There was no history of pigmenturia. At age 49, she could walk only about 50 m before experiencing fatigue and myalgia. An initial syndromic diagnosis of chronic fatigue was considered before further evaluation in our center for neuromuscular disease. There was a mild thoracic kyphoscoliosis, bilateral mild ptosis, and a mild early external ophthalmoplegia. There was mild (Medical Research Council [MRC] 5−/5) weakness of her neck flexion and symmetric proximal limb weakness of MRC grade 5−/5 in arms and legs. Repetitive testing caused rapid power fatigue. The degree of fatigue and disability experienced by this patient was severe …