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

• Published in: Journal of inherited metabolic disease 2013-11, Vol.36 (6), p.989-995
• Main Authors: Borroni, Barbara, Cotelli, M. S., Premi, E., Gazzina, S., Cosseddu, M., Formenti, A., Gasparotti, R., Filosto, M., Padovani, A.
• Format: Article
• Language: English
• Subjects: Adult; Age; Age of Onset; Biochemistry; Biological and medical sciences; Brain - pathology; Brain - physiopathology; Carbohydrates (enzymatic deficiencies). Glycogenosis; Case-Control Studies; Errors of metabolism; Female; Functional Neuroimaging - methods; Glycogen Storage Disease Type II - diagnosis; Glycogen Storage Disease Type II - epidemiology; Glycogen Storage Disease Type II - pathology; Human Genetics; Humans; Internal Medicine; Magnetic Resonance Imaging; Male; Medical genetics; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Middle Aged; Neuropsychological Tests; Original Article; Pediatrics
• ISSN: 0141-8955; 1573-2665
• DOI: 10.1007/s10545-013-9601-7

Background 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. Objective Our objective in this study was to assess brain changes in late-onset GSD II. Methods 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. Results 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. Conclusions 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.