INTRODUCTION: Severe exercise limitation in young adults due to mitochondrial myopathy is extremely rare, approximately 6 per 100,000. Usually affecting the most oxygen dependent organ systems, ie nervous system, rarely isolated proximal muscle myopathy and exercise intolerance could be the presenting symptoms. We report a case of a 25 year old lady who presented with 9 months of dyspnea and progressive exertional fatigue due to mitochondrial myopathy.
CASE PRESENTATION: A 25 year old woman with past medical history of childhood asthma presented with progressive dyspnea on exertion and 2 episodes of syncope. Her work up was started with assessment of 6 minute walk test and pulmonary function tests that revealed desaturation to 79% and symptom limitation at 240 meters, and unremarkable pulmonary function tests. Cardiac arrhythmia was also a concern given her syncopal episodes and a 48-hr Holter Monitor showed 1-2 episodes of atrial tachycardias per hour. Patient’s dyspnea continued to get worse and she began to develop shortness of breath at rest, requiring help with all activities of daily living. Rest and exercise echocardiograms were performed to assess for cardiac function, congenital anomolies as well as assessment of pulmonary artery pressures, which showed a mild elevation in PASP of 37. Her treadmill stress echocardiogram showed normal ejection fraction of 60-65%. She has also had a CT angiogram, high resolution chest CT, V/Q scan, and thorough rheumatological work up that has been unrevealing. This was followed by noninvasive and invasive exercise studies with a PA catheter to assess her limitations of activity. Further history also revealed difficulty with getting up from a seated position, and fatigue with simple activities such as brushing her hair. She has had difficulty with exercise since childhood that was attributed to childhood asthma. Her family history is significant for a maternal cousin with similar complaints. Invasive cardiopulmonary exercise study showed significantly decreased peak oxygen consumption of 0.86 L/min (48% predicted) and increased oxygen consumption for the given work load. ABG and lactic acid levels reveal passing of lactate threshold during unloaded exercise to peak level 10.4, which is indicative of severe defect in oxygen uptake/utilization by the muscles and presence of a peripheral respiratory chain disorder. A repeat echocardiogram to reassess cardiac function has reconfirmed normal cardiac function. Preliminary results from a subsequent muscle biopsy are consistent with mitochondrial myopathy.
DISCUSSIONS: Mitochondrial myopathies have a variety of clinical presentations usually involving neurologic complaints and cardiac deficits, however very rarely present as isolated exercise intolerance and severe weakness. They can be classified based on nuclear or mitochondrial DNA mutations, without clear genotype-phenotype correlations. Mitochondrial myopathy should be considered in the work up of severe shortness of breath and exercise limitation if more common etiologies such as IPAH, congenital cardiac anomalies, cardiomyopathy and interstitial lung disease are ruled out. The mainstay of treatment is supportive including respiratory care such as BIPAP, CPAP or tracheostomy. A thorough ophthalmologic, neurologic and cardiac assessment should be done to assess for possible defects in such patients. Pharmacologic therapy has not been proven to be effective. A muscle biopsy would show the mutant mitochondrial DNAs accumulate preferentially in ragged-red fibers.
CONCLUSION: This is a very rare presentation for a very rare disease. Mitochondrial myopathy should be considered in young adults who present with severe shortness of breath, exercise limitation and weakness. Although there are no specific treatments, supportive measures, mild exercise, coenzyme Q10, creatine and L-carnitine are recommended.
DISCLOSURE: Arin Aboulian, No Financial Disclosure Information; No Product/Research Disclosure Information