Résumé :
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In late-onset acid-maltase deficiency (LO-GSDII), evolution is generally slow and complicates evaluation. We report the case of a 43yr-old woman, in whom NMRI evidenced localised but dramatic degradation of quadriceps muscles over a 3yr period, despite ongoing enzyme replacement therapy (ERT) with glucosidase alfa (IV infusion 20 mg/kg every other week). Clinical onset was at age 18. Between diagnosis at 31yrs and ERT onset at 39yrs, comparative scanner evidenced severe degradation of glutei muscles and apparition of fatty infiltration in quadriceps and hamstrings. Spin-echo T1-weighted NMRI at +5 , +31 and +39 months into ERT showed further destruction of thigh muscles, most spectacularly in quadriceps (Fig. 1). Quantitation showed increases in number of fat pixels of up to 40% in semi-tendinous and 32% in vastus lateralis muscles, while distal leg muscles were preserved.In parallel, knee extension strength measured by quantitative muscle isometric dynamometry (Biodex Medical, USA) decreased by 32% on both sides. Muscle glycogen measured by in vivo C-13 NMR spectroscopy1 failed to decrease in the left thigh from 5mths pre-ERT to +27mths, while it increased to above normal in calf muscles between +25mths and +39mths. Clinically, knee extensor muscles manual testing score remained stable at 3. The 6-min walk test was 285m at baseline, 270m at +26mths, 255m at +37mths; the motor functional scale MFM was stable (72%; 69%; 72%) over the same period, as was sitting vital capacity (2,47L; 2,69L; 2.36L). Functional abilities remained unchanged (walking unaided indoors and with a cane outdoors, banister needed for climbing stairs). ERT was well tolerated. IgG antibodies peaked at 12800 at +37mths into ERT, but since re-declined to 6400. Test for inhibitory antibodies to rhGAA was negative.Skeletal muscle response to first generation ERT in LO-GSDII has been mitigated. Quantitative imaging in patients undergoing ERT showed 5% increase in thigh muscle volume but concomitant 4% increase in intramuscular fat2. To the best of our knowledge such a brutal degradation in muscle condition in a single patient has not been previously described. Degradation in LO-GSDII may thus be very rapid and muscle specific, and difficult to detect by clinical examination and manual testing. Regular whole-body or lower-limb NMRI can improve follow up of individual patients.1. C. Wary, et al., Neuromuscul Disord., 2003. 13. 545.2. S. Ravaglia, et al., J Inherit Metab Dis, 2010. 33. 737.
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