Purpose of review: This review highlights recent contributions regarding clinical heterogeneity, pathogenic mechanisms, therapeutic trials, and animal models of the muscle glycogenoses.
Recent findings: Most recent publications have dealt with the clinical effects of enzyme replacement therapy (ERT) in glycogenosis type II (Pompe disease), including the cognitive development of children with the infantile form who have reached school age. Standardized exercise testing has shown the similarity between McArdle disease and one of the most recently described muscle glycogenoses, phosphoglucomutase deficiency. Cycle ergometry in patients with glycogenosis type III (debrancher deficiency) without overt weakness has documented exercise intolerance relieved by glucose infusion, consistent with the glycogenolytic block. A mouse model of McArdle disease faithfully recapitulates most features of the human disease and will prove valuable for a better understanding of pathogenesis and therapeutic modalities. Polyglucosan body myopathy with cardiomyopathy has been associated with mutations in RBCK1, a ubiquitin ligase, which have also been reported in children with early-onset immune disorder. The role of polyglucosan storage in muscle and in both central and peripheral nervous systems has been confirmed in the infantile and late-onset forms of glycogenosis type IV (brancher enzyme deficiency). Additional novel findings include the involvement of the heart in one patient with phosphofructokinase (PFK) deficiency and the presence of tubular aggregates in a manifesting heterozygote with phosphoglycerate mutase deficiency.
Summary: Important recent developments in the field of muscle glycogenoses include a new disease entity, a new animal model of McArdle disease, and better knowledge of the pathogenesis in some glycogenoses and of the long-term effects of enzyme replacement therapy in Pompe disease.