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 treelike 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 glycogen storage disease. 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 pharmacological amounts of glucocorticoids.
There are more than 12 forms of glycogenoses (see Fig.
154-1). The glycogen found in these disorders is abnormal in
quantity or quality, or both. Historically, the glycogen storage
diseases 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.
Liver and muscle have abundant glycogen and are the most commonly
and seriously affected tissues. The glycogen storage diseases that
principally affect the liver (see Fig. 154-1) 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 synthetase deficiency (type 0), and glucose transporter-2
defect (type XI). Because carbohydrate metabolism in the liver affects
plasma glucose levels, the disorders of hepatic glycogen degradation
and glucose release typically cause fasting hypoglycemia and hepatomegaly.
Some glycogen storage diseases are associated with liver complications;
for example, hepatic adenomas with risk for malignant transformation
in GSD I and liver cirrhosis with risk for progression to end-stage
liver failure or malignancy (types III, IV, and some forms of type
IX). Other organs besides liver may also be involved; for example, renal
dysfunction in glycogen storage disease type I; cardiac involvement
in types II, III, and IX; myopathy ...