VP.34 Two-year follow-up of muscle strength and function in patients with glycogen storage disease type IIIa

Abstract

Glycogen storage disease type IIIa (GSDIIIa) is an autosomal recessive disorder caused by mutations in the AGL gene coding for the glycogen debranching enzyme. The symptoms start in childhood with liver involvement and progress at adulthood with skeletal muscle weakness. With imminent therapeutic trials, quantitative documentation of disease progression is essential. The objective of this study is to identify the most affected skeletal muscle measures over 2 years of follow-up. The 6-minutes walk test (6MWT), knee (Biodex torquemeter) and ankle (MyoAnkle dynamometer) flexion/extension torques, as well as muscle function measure (MFM) were performed at 2 years interval. Forty-one patients aged from 10 to 66 years old (28±15 y), 59% females, were included. At baseline, the 6-minute walk distance (6MWD), knee and ankle flexion/extension torques, expressed as a percentage of predicted value (%pred), as well as the 3 dimensions of the MFM (D1, D2, D3) and the MFM total score, were all significantly lower than the maximum score of 100% (P<0.01). This reflects significant impairment in walking, knee and ankle joints muscle strength, standing and transfers (MFM D1), axial and proximal (MFM D2) and distal (MFM D3) motricity. After 2-years of follow-up, only MFM D1 and the MFM total score were slightly but significantly reduced (paired Wilcoxon test, P=0.016 and P=0.010, respectively). Because the age of onset of MFM D1 degradation was previously established around 35 years (Decostre 2017), the paired Wilcoxon test was performed only for patients aged at least 34 years (n=15). In this small sample, MFM D3 and knee extension strength were significantly impaired (P<0.05), but not MFM D1 (probably because 2 patients improved their MFM D1 score). In conclusion, the MFM and the knee extension strength are the most promising outcome measures for this slowly progressive disease. A longer follow-up is ongoing.