Recent advances and current clinical perspectives in the diagnosis and treatment of glycogenosis type II

Abstract

Glycogenosis type II (GSDII), or acid maltase deficiency, is a disorder affecting skeletal and cardiac muscle and is caused by a deficiency of acid alpha-glucosidase (GAA). The disease encompasses a wide spectrum of clinical presentations, ranging from very severe cases presenting soon after birth (the “classic” infantile form) to milder, late-onset cases. Infant patients show a rapidly progressive course of the disease, with muscle weakness, hypertrophic cardiomyopathy, and death usually before the first year of age; alpha-glucosidase is virtually absent. Affected children and adults show a more slowly progressing myopathy with decreased limb strength and often impaired respiratory muscle function. The adult-onset form was first recognized by Engel.1 Variable levels of GAA were described in muscle and leukocytes from patients with infantile, childhood, and adult forms by Engel and Angelini,2 whereas morphologic and biochemical abnormalities were also found in adult-cultured fibroblasts,3 showing the multisystemic involvement of the enzyme defect. In this educational supplement, two articles describe this prototypic lysosomal disorder. The first article deals with the diagnosis of GSDII, and the second, by the same group of authors, is about suggested management to achieve the best medical practice. Although a rare disease, adult-onset GSDII can be challenging for many neurologists, because advances in the diagnosis and long-term treatment are relevant issues. The exact diagnosis of late-onset GSDII is still a controversial problem, because histopathologic, biochemical, and molecular studies of such patients are needed. Late-onset GSDII diagnosis may be difficult and missed on a routine muscle biopsy as pathology could be normal in certain muscles or be mild or not noted.4 Therefore, the combined use of muscle histopathology, …