19 Glycogen Storage Diseases
Introduction
• Glycogen storage diseases are caused by deficiencies of enzymes that regulate the
synthesis or degradation of glycogen.
• Glycogen, a polysaccharide composed of glucose units, is the main carbohydrate
reserve in the body.
• This polysaccharide is assembled through a process of chain elongation and
branching by the sequential addition of glucose units, achieved by glycogen
synthetase and branching enzymes.
Glycogenolysis
Catabolism of the
polysaccharide is achieved by
the opposite process, through
phosphorylase and
debranching enzymes
•
Importance of Glycogen
• Glycogen is abundant in the liver, where it is used predominantly to form blood
glucose, and in muscle, where it is a fuel for muscle contraction.
• The brain, on the other hand, although utilizing glucose preferentially for its
metabolic needs, does not store glycogen to any significant extent.
• Hence, the brain is dependent on receiving glucose from the blood supply
Types of GSD
• The syndromes of glycogen storage disease can be divided into at least eight
different types with respect to clinical and chemical manifestations and according
to the enzymatic deficiency.
• Most of the various types affect the liver and are a consequence of deficient
activity of an enzyme directly involved in degradation of glycogen to glucose-
6phosphate, or rarely, the synthesis of glycogen from glucose-6-phosphate
Incidence of GSD
• There is a wide range of incidence in the occurrence of glycogen storage diseases.
• The more common glycogen storage disease, type I, occurs about once in every
100,000 births.
• Frequency of the less common forms such as type II has not yet been determined.
Glycogen Storage Disease Type I
• the most commonly diagnosed type
• GSD I is characterized by a deficiency of the enzyme glucose-6-phosphatase
• The inability to dephosphorylate glucose-6-phosphate results in hypoglycemia and
its metabolic consequences.
Consequences
• Risk of death or hypoglycemic damage to the brain in early infancy
• The most constant and life-threatening feature of this disease is the low blood
glucose levels which result from relatively short periods of fasting.
• Fasting for as little as 2 to 4 hours is almost always associated with a decrease in
blood glucose to less than 70 mg/dL
• It is not uncommon to observe 6- to 8-hour fasting levels of 5 to 10 mg/dL
• In patients with GSD I, it is possible to degrade glycogen to glucose-6phosphate,
but, in the absence of the glucose-6- phosphatase enzyme, no glucose is released
and blood glucose levels continue to fall.
• The liver is further stimulated, which leads to continued glycogen degradation
resulting in secondary manifestations of GSD I that cause the characteristic
elevations in blood lipids, lactate, and uric acid.
• Hepatomegaly is often present at birth and can progress to huge enlargement of the
liver if the disease is poorly controlled. This enlargement is due to the
accumulation of glycogen.
• The chronic lactic acidosis with elevated glucagon and low insulin levels seems to
be related to the poor growth seen in children with this condition.
• Bones may be osteoporotic, and some patients show delayed bone age associated
with an increased phosphate loss coupled with the acidosis.
Dietary Intervention
• Dietary manipulation has evolved as the preferred method of management for this
condition.
• Frequent oral feedings, high in carbohydrate, are recommended to maintain blood
glucose levels above 70 mg/dL.
• The use of uncooked cornstarch has been introduced due to its ability to maintain
blood glucose levels over an extended period of time.
• The cornstarch is slowly digested by the body, allowing for the gradual release of
glucose. This helps the individual to maintain a fed state for an extended period of
time, from about 3 to 6 hours.
• The typical regimen of cornstarch consists of 1 to 2 grams cornstarch per kilogram
body weight per dose, administered every 3 to 6 hours.
• Some individuals have even been able to forgo nocturnal feedings by ingesting
cornstarch at bedtime and once in the middle of the night.
• Cornstarch should not be mixed in beverages containing citric acid, nor should it
be heated, because that will result in a breakdown in the starch molecules that
allows more rapid digestion and interferes with the release of glucose over an
extended time period
Sick days
• Total parenteral nutrition or continuous nasogastric infusions of glucose correct
most of the metabolic abnormalities associated with GSD I.
• The impracticality of these forms of management, however, led to the
development of a dietary treatment plan that includes frequent daytime meals
followed by continuous drip nocturnal enteral feedings.
• Hypoglycemia and death have been reported following malfunctions of the pump
or dislodging of the tube
Treatment Goals
• The goals of nutritional therapy for GSD I are to prevent
– hypoglycemia
– correct metabolic balance
– provide optimal nutrition to support growth and development.
• Carbohydrates from complex sources should provide about 60% to 70% of the
total caloric intake.
• A portion of the carbohydrate may be provided by the uncooked cornstarch.
• Protein should come from lean sources, providing 10% to 15% of total kcal.
• Fat should provide less than 30% of total kcal, and dietary saturated fat should be
limited.
• Two-thirds of the kcal will be given during daytime feedings to allow for
carbohydrates to be distributed frequently and evenly over the 24-hour period.
• One-third of kcal are administered overnight, primarily from a carbohydrate
source via cornstarch or tube feedings.
• Meals high in starch, without free glucose, tend to provide a more sustained
increase in blood glucose levels
• Except during symptoms suggestive of hypoglycemia, glucose solutions alone are
not recommended.
