Physical therapy assessment and whole-body magnetic resonance imaging findings in children with glycogen storage disease type IIIa: A clinical study and review of the literature

Mol Genet Metab. 2021 Nov;134(3):223-234. doi: 10.1016/j.ymgme.2021.10.002. Epub 2021 Oct 9.


Introduction: Early recognized manifestations of GSD III include hypoglycemia, hepatomegaly, and elevated liver enzymes. Motor symptoms such as fatigue, muscle weakness, functional impairments, and muscle wasting are typically reported in the 3rd to 4th decade of life.

Objective: In this study, we investigated the early musculoskeletal findings in children with GSD IIIa, compared to a cohort of adults with GSD IIIa.

Methods: We utilized a comprehensive number of physical therapy outcome measures to cross-sectionally assess strength and gross motor function including the modified Medical Research Council (mMRC) scale, grip and lateral/key pinch, Gross Motor Function Measure (GMFM), Gait, Stairs, Gowers, Chair (GSGC) test, 6 Minute Walk Test (6MWT), and Bruininks-Oseretsky Test of Motor Proficiency Ed. 2 (BOT-2). We also assessed laboratory biomarkers (AST, ALT, CK and urine Glc4) and conducted whole-body magnetic resonance imaging (WBMRI) to evaluate for proton density fat fraction (PDFF) in children with GSD IIIa. Nerve Conduction Studies and Electromyography results were analyzed where available and a thorough literature review was conducted.

Results: There were a total of 22 individuals with GSD IIIa evaluated in our study, 17 pediatric patients and 5 adult patients. These pediatric patients demonstrated weakness on manual muscle testing, decreased grip and lateral/key pinch strength, and decreased functional ability compared to non-disease peers on the GMFM, 6MWT, BOT-2, and GSGC. Additionally, all laboratory biomarkers analyzed and PDFF obtained from WBMRI were increased in comparison to non-diseased peers. In comparison to the pediatric cohort, adults demonstrated worse overall performance on functional assessments demonstrating the expected progression of disease phenotype with age.

Conclusion: These results demonstrate the presence of early musculoskeletal involvement in children with GSD IIIa, most evident on physical therapy assessments, in addition to the more commonly reported hepatic symptoms. Muscular weakness in both children and adults was most significant in proximal and trunk musculature, and intrinsic musculature of the hands. These findings indicate the importance of early assessment of patients with GSD IIIa for detection of muscular weakness and development of treatment approaches that target both the liver and muscle.

Keywords: 6-minute walk test; BOT-2; GMFM; GSD III; GSGC; Glycogen storage disease type III; Hand grip strength; Lateral key pinch; Muscle function; Muscle strength; PT; Physical therapy; WBMRI; Whole-body magnetic resonance imaging.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Cohort Studies
  • Cross-Sectional Studies
  • Female
  • Glycogen Storage Disease Type III / diagnostic imaging*
  • Humans
  • Infant
  • Infant, Newborn
  • Magnetic Resonance Imaging / methods
  • Magnetic Resonance Imaging / statistics & numerical data*
  • Male
  • Middle Aged
  • Muscle Weakness / pathology
  • Muscle, Skeletal / pathology
  • Physical Therapy Modalities / standards*
  • Whole Body Imaging / standards
  • Whole Body Imaging / statistics & numerical data*
  • Young Adult

Supplementary concepts

  • Glycogen Storage Disease IIIA