P.74 Using high-field magnetic resonance spectroscopy to measure muscle glycogen in patients with McArdle disease

Abstract

Glycogen plays a critical role as an energy source in skeletal muscle. McArdle disease is a recessively inherited disorder in which muscle glycogen breakdown is blocked due to myophosphorylase deficiency. The patients suffer from severe exercise intolerance marked by premature fatigue with muscle contractures and episodic rhabdomyolysis. Additionally, some patients show progressive muscular atrophy when they get older, mainly in lumbar paraspinal muscles but not in thigh or calf muscles. The cause of fat replacement in older McArdle patients is unknown but could relate to a higher glycogen accumulation in their muscles. Utilizing the high sensitivity of 13C magnetic resonance spectroscopy at 7 Tesla field strength, we wanted to quantify muscle glycogen in lumbar, thigh and calf muscles in young McArdle patients as well as healthy controls to test the hypothesis of variable glycogen content in muscles of patients with McArdle disease. Preliminary results from 5 patients and 8 controls, show increased muscle glycogen concentration in the calf (4.4 times normal levels, p = 0.002), hamstrings (2.7 times normal levels, p = 0.02) and anterior thigh compartment (3.2 times normal levels, p = 0.01), while there was no difference in the lumbar muscle glycogen content vs. healthy (p = 0.6). No clear pattern of muscle glycogen distribution was seen in neither the McArdle nor the control groups. Our results are in line with previous studies in that we see a 3-5 times increase in glycogen compared to control. Surprisingly, this is not seen in the lumbar muscle group, which is the muscle group most prone to fat replacement with age. Thus, it does not appear that a difference in glycogen concentration between muscles of McArdle patients can explain the fat replacement seen in specific muscles groups of older patients.