Title:Late-Onset Glycogen Storage Disease Type 2
VOLUME: 14 ISSUE: 8
Author(s):M. Filosto, M.S. Cotelli, V. Vielmi, A. Todeschini, F. Rinaldi, S. Rota, M. Scarpelli and A. Padovani
Affiliation:Clinical Neurology, University Hospital "Spedali Civili", Pz.le Spedali Civili 1, 25100 Brescia, Italy.
Keywords:Autophagia, enzymatic replacement therapy, glycogenosis II, glycogen storage disease, GAA, GSDII,
lysosomal disease, Pompe’s disease.
Abstract:Glycogenosis II (GSDII) is an autosomal recessive lysosomal storage disorder resulting from acid
alpha-glucosidase (GAA) deficiency, subsequent lysosomal accumulation of glycogen in muscles, impairment
of autophagic processes and progressive cardiac, motor and respiratory failure. The infantile form usually
appears in the first month of life, progresses rapidly and presents with severe cardiac involvement and
complete deficiency of alpha-glucosidase activity (< 1% of normal controls). The late-onset form is
characterized by great variability of the phenotypical spectrum. Main findings are muscle weakness and severe
respiratory insufficiency while cardiac involvement may be completely absent. Residual GAA enzyme activity
may correlate with severity of phenotype but many adult patients sharing the same mutations present with a
wide variability in residual enzyme activity, age of onset and rate of disease progression, thus supporting a role
for other factors, i.e., post-translational modifications and modifier genes, in modulating disease presentation.
Enzyme replacement therapy (ERT) with alglucosidase alfa stabilizes the disease or improves muscle and/or
respiratory function. However, efficacy of ERT may be influenced by several factors including age when ERT
begins, extent of muscle damage, degree of defective autophagy, diversity in muscle fiber composition,
difficulties in delivery of the therapeutic agent and antibody production. Further studies should be warranted to
investigate factors determining the differences in clinical expression and therapeutic response in order to
achieve better clinical and therapeutic management of these patients.
