Journal of Inherited Metabolic Disease

, Volume 36, Issue 6, pp 989–995 | Cite as

The brain in late-onset glycogenosis II: a structural and functional MRI study

  • Barbara Borroni
  • M. S. Cotelli
  • E. Premi
  • S. Gazzina
  • M. Cosseddu
  • A. Formenti
  • R. Gasparotti
  • M. Filosto
  • A. Padovani
Original Article



Late-onset glycogenosis type II (GSD II) is a rare, multisystem disorder mainly affecting limb and respiratory muscles due to acid alpha glucosidase deficiency. Despite evidence at autopsy of glycogen accumulation in the brain, no study exploring brain functions is yet available.


Our objective in this study was to assess brain changes in late-onset GSD II.


Each patient underwent a standardized neuropsychological assessment, regional grey-matter (GM) atrophy, and resting-state functional magnetic resonance imaging (RS-fMRI). Functional connectivity maps of the salience (SN) and default-mode (DMN) networks were considered. A group of age- and gender-matched healthy controls was enrolled for MRI comparisons. P values family-wise error (FWE) cluster level corrected inferior to 0.05 were considered.


Nine GSD II patients (age 46.6 ± 8.0; 55 % male) were recruited. No significant GM atrophy was found in patients compared with controls (n = 18; age 48.0 ± 9.8,;40 % male). Functional connectivity within the SN was selectively reduced in patients, and cingulate gyrus and medial frontal cortex were mainly involved. Accordingly, patients had significant impairment of executive functions (as measured by Wisconsin Card Sorting test), whereas other cognitive domains were within mean normal ranges.


Our findings extend the clinical spectrum of GSD II by indicating that brain changes occur in this muscular disorder. Above all, these results should lead to better examinations of therapeutic approaches and perspectives for the affected patients. Further studies evaluating in depth these issues are warranted.


Functional Connectivity Enzyme Replacement Therapy Glycogen Storage Disease Pompe Disease Salience Network 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors kindly thank Prof. C. Danesino from the Unit of Medical Genetics of University of Pavia, Italy, for conducting the genetic studies, and Dr. P. Tonin from the Department of Neurological, Neuropsychological, Morphological and Movement Sciences of University of Verona, Italy, for biochemical assay. We also thank the Italian Group for Glycogenosis II of the Italian Association of Myology.

Conflict of interest



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Copyright information

© SSIEM and Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Barbara Borroni
    • 1
  • M. S. Cotelli
    • 1
  • E. Premi
    • 1
    • 2
  • S. Gazzina
    • 1
  • M. Cosseddu
    • 1
  • A. Formenti
    • 1
  • R. Gasparotti
    • 3
  • M. Filosto
    • 1
  • A. Padovani
    • 1
  1. 1.Neurology UnitUniversity of BresciaBresciaItaly
  2. 2.Neurology UnitValleCamonica HospitalBresciaItaly
  3. 3.Neuroradiology UnitUniversity of BresciaBresciaItaly

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