Glycogen, the storage form of glucose in animal cells, is composed of glucose residues joined in straight chains by α–1,4 linkages and branched at intervals of 4 to 10 residues with α–1,6 linkages. The tree-like molecule can have a molecular weight of many millions and may aggregate to form structures recognizable by electron microscopy. In muscle, glycogen forms β particles, which are spherical and contain up to 60,000 glucose residues. Each β particle contains a covalently linked protein called glycogenin. Liver contains β particles and rosettes of glycogen called α particles, which appear to be aggregated β particles.
The primary function of glycogen varies in different tissues. In skeletal muscle, stored glycogen is a source of fuel that is used for short-term, high-energy consumption during muscle activity; in the brain, the small amount of stored glycogen is used during brief periods of hypoglycemia or hypoxia as an emergency supply of energy. In contrast, the liver takes up glucose from the bloodstream after a meal and stores it as glycogen. When blood glucose levels start to fall, the liver converts glycogen back into glucose and releases it into the blood for use by tissues such as brain and erythrocytes that cannot store significant amounts of glycogen.
Glycogen storage diseases (GSDs) are inherited disorders that affect glycogen metabolism. Disorders in virtually every enzyme involved in the synthesis or degradation of glycogen and its regulation cause some type of GSD. Excluded from this section are those conditions in which tissue glycogen accumulation is secondary, such as overtreatment of diabetes mellitus with insulin or administration of pharmacologic amounts of glucocorticoids.
There are more than 12 forms of glycogenosis (Fig. 149-1). The glycogen found in these disorders is abnormal in quantity or quality or both. Historically, the GSDs were categorized numerically in the order in which the enzymatic defects were identified. This section classifies the diseases by the organs involved and the clinical manifestations.
Metabolic pathways related to glycogen storage diseases and to galactose and fructose disorders. Nonstandard abbreviations are as follows: G, glycogenin, the primer protein for glycogen synthesis; GSa, active glycogen synthase; GSb, inactive glycogen synthase; Pa, active phosphorylase; Pb, inactive phosphorylase; PaP, phosphorylase a phosphatase; pbKa, active phosphorylase b kinase; PbKb, inactive phosphorylase b kinase. (Modified with permission from Isselbacher KJ, Martin JB: Harrison’s Principles of Internal Medicine, 13th ed. New York: McGraw-Hill; 1994.)
Liver and muscle have abundant glycogen and are the most commonly and seriously affected tissues. The GSDs that principally affect the liver (see Fig. 149-1) include glucose-6-phosphatase deficiency (type I), debranching enzyme deficiency (type III), branching enzyme deficiency (type IV), liver phosphorylase deficiency (type VI), phosphorylase kinase deficiency (type IX), liver glycogen synthase deficiency (type 0), and glucose transporter-2 defect (type XI). Because carbohydrate metabolism ...