Abstract
BACKGROUND: Late-onset Pompe disease has a characteristic pattern of fat replacement and wasting of especially axial and hamstring muscles. This characteristic pattern of muscle degeneration is still to be explained but could relate to differences in how glycogen is deposited in the different muscles. This cross-sectional observational study investigates the glycogen levels of different muscle groups in young late-onset Pompe subjects and matched controls. METHODS: (13)C-MR Spectroscopy at 7 Tesla field strength was used to quantify glycogen concentration in four muscle groups: the calf, hamstring, anterior thigh and lumbar muscles of patients with late-onset Pompe disease and healthy controls. An unpaired t-test with correction for multiple comparisons was used to test the difference between Pompe subjects and healthy controls for each muscle area. RESULTS: 11 late-onset Pompe patients (6 female, mean age 31, range 20-44) and 16 healthy volunteers (10 female, mean age 27, range 19-35) were included. We found that Pompe subjects had 1.8 (95% CI 1.56 to 2.16) times more glycogen in hamstring muscles (p≤0.001) and 2.2 (95% CI 1.24 to 2.48) times more in lumbar muscles (p≤0.004), 1.4 (95% CI 1.07 to 1.73) times more in the anterior thigh muscles (p=0.045) while levels were similar to healthy persons in the calf (95% CI 0.83 to 1.12, p=0.7). CONCLUSIONS: The first muscles to degenerate in Pompe disease are hamstring and paraspinals. Our findings, therefore, suggest that high glycogen levels precede fatty degeneration of muscles, and that monitoring glycogen levels could be an important biomarker to assess treatment effect in Pompe disease.