Long term longitudinal study of muscle function in patients with glycogen storage disease type IIIa

• Published in: Molecular genetics and metabolism 2017-11, Vol.122 (3), p.108-116
• Main Authors: Decostre, Valérie, Laforêt, Pascal, De Antonio, Marie, Kachetel, Kahina, Canal, Aurélie, Ollivier, Gwenn, Nadaj-Pakleza, Aleksandra, Petit, François M., Wahbi, Karim, Fayssoil, Abdallah, Eymard, Bruno, Behin, Anthony, Labrune, Philippe, Hogrel, Jean-Yves
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Cross-Sectional Studies; Debranching enzyme deficiency; Female; Glycogen storage disease type III; Glycogen Storage Disease Type III - complications; Glycogen Storage Disease Type III - genetics; Glycogen Storage Disease Type III - physiopathology; Hand Strength; Humans; Longitudinal Studies; Male; Metabolic myopathy; Middle Aged; Muscular Diseases - complications; Muscular Diseases - etiology; Muscular Diseases - physiopathology; Outcome and Process Assessment (Health Care); Outcome measures; Retrospective Studies; Time Factors; Young Adult
• ISSN: 1096-7192; 1096-7206
• DOI: 10.1016/j.ymgme.2017.08.010

Glycogen storage disease type III (GSDIII) is an autosomal recessive disorder caused by mutations in the AGL gene coding for the glycogen debranching enzyme. Current therapy is based on dietary adaptations but new preclinical therapies are emerging. The identification of outcome measures which are sensitive to disease progression becomes critical to assess the efficacy of new treatments in upcoming clinical trials. In order to prepare future longitudinal studies or therapeutic trials with large cohorts, information about disease progression is required. In this study we present preliminary longitudinal data of Motor Function Measure (MFM), timed tests, Purdue pegboard test, and handgrip strength collected over 5 to 9years of follow-up in 13 patients with GSDIII aged between 13 and 56years old. Follow-up for nine of the 13 patients was up to 9years. Similarly to our previous cross-sectional retrospective study, handgrip strength significantly decreased with age in patients older than 37years. MFM scores started to decline after the age of 35. The Purdue pegboard score also significantly reduced with increasing age (from 13years of age) but with large inter-visit variations. The time to stand up from a chair or to climb 4 stairs increased dramatically in some but not all patients older than 30years old. In conclusion, this preliminary longitudinal study suggests that MFM and handgrip strength are the most sensitive muscle function outcome measures in GSDIII patients from the end of their third decade. Sensitive muscle outcome measures remain to be identified in younger GSDIII patients but is challenging as muscle symptoms remain discrete and often present as accumulated fatigue. •Muscle outcomes measures are needed in glycogen storage disease type III.•Muscle outcomes were followed over 5 to 9years in 13- to 56-years old patients.•Purdue pegboard score was age-dependant despite large inter-visit variability.•Handgrip strength and MFM scores become age sensitive late in the third decade.•Timed tests results worsened dramatically in some patients older than 30years old.