Inherited deficiency of acid alpha-glucosidase (acid maltase, GAA) leads to glycogen storage disease type II. Clinical manifestations and prognosis of the disease depend on the age of onset and tissue involvement. GAA deficiency is extremely heterogeneous, ranging from a rapidly progressive fatal infantile-onset form to a slowly progressive adult-onset myopathy associated with respiratory insufficiency. Biochemical and immunochemical studies of the biosynthesis of the enzyme in GAA-deficient patients established the molecular diversity of the disease. Cloning and sequencing of the cDNA and the gene provided the basis for genetic analysis of the patients with different phenotypes. In this article, we summarize the data on mutations in the GAA gene and discuss the correlation between the genotype and phenotypic expression of the disease.