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WHAT IS GLYCOGEN
STORAGE DISEASES
(GSD) ?
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GSD has 2 classes of cause :
(a) Genetic
(b) Acquired
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-Caused
by a genetic enzyme defect that is
inherited from both parents.
-Normally, enzymes help convert glucose into
glycogen for storage and other enzymes
convert the glycogen back to glucose when
quick energy is needed, like during exercises.

In a person with a GSD, some of these enzymes
are defective.
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This causes the build up of abnormal and types
of glycogen in liver and/or muscle tissues.

In livestock , acquired
GSD is caused by
intoxication with the
alkaloid castanospermine.
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Low blood sugar.
Enlarged liver.
Slow growth.
Muscle cramps.
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Also known as ‘’VON – GIERKE’S DISEASE’’.
GSD Type 1 is the most common of the GSD
and accounts for 90% of all GSD cases.
It is results from deficiency of the enzyme
glucose-6-phosphatase.
This deficiency impairs the ability of the
liver to produce glucose from glycogen.
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Since these are the two principal
metabolic mechanisms by which the
liver supplies glucose to the rest of the
body during periods of fasting, it
causes severe hypoglycemia (
deficiency of glucose in bloodstream).
Reduced glycogen breakdown results
in increased glycogen storage in liver
and kidneys, causing enlargement of
both.
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Enlarged liver and kidneys.
Low blood sugar.
High levels of uric acid in the
blood.
Impaired growth and delayed
puberty.
Bone thinning from osteoporosis.
Increased mouth ulcers and
infection.

Frequent or continuous feedings
of cornstarch or other
carbohydrates are the principal
treatment.
GLYCOGEN STORAGE
DISEASES (GSD) TYPE II
?
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Pompe’s disease also referred to as Glycogen Storage
Disease Type II or acid maltase deficiency, is an
autosomal recessive disorder of glycogen metabolism
caused by a deficiency of the lysosomal enzyme acid
glucosidase.
People affected with this disease are unable to degrade
glycogen stored in the lysosome and thus leading to
the accumulation of glycogen in lysosomal storage
vacuoles.
Pompe’s disease has been divided into three forms defined
by age of onset and progression of symptoms.
 The three forms include infantile onset, juvenile onset and
adult onset.
 In the infantile form of the disease, patients display cardiac
impairment, which is fatal before two years of life.
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Patients with juvenile or adult forms can present
diaphragm involvement leading to respiratory failure.
The adult onset symptoms involve generalized muscle
weakness and wasting of respiratory muscles in the
trunk, lower limbs, and diaphragm.
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Glycogen is mostly found in the liver and
skeletal muscles.
The polymer is composed of units of glucose
linked α-1-4 with branches occurring at a-16, approximately every 8-12 residues.
The end of the molecule containing a free
carbon number one on glucose is called a
reducing end. The other ends are all called
non-reducing ends
http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=stryer.figgrp.2912
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Glycogen molecules are very large in size
Therefore inability to degrade them results
to a large accumulation of normal structure
in the lysosomes of all cells. The excess
storage of glycogen in the vacuoles is the
consequence of defects in the lysosomal
hydrolase.
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The acid a-glucosidase normally designated as GAA
gene.
Glycogen storage disease type II has been shown to be
caused by missense, nonsense and splice-site
mutations, partial deletions and insertions. Some
mutations are specific to certain ethnic groups.
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The normal function of acid a-glucosidase is
to hydrolyze both a-1,4- and a-1,6glucosidic linkages at acid Ph.
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The activity of the enzyme leads to the
complete hydrolysis of glycogen which is its
natural substrate.
As would be expected from this activity,
deficiency in acid a-glucosidase leads to the
accumulation of structurally normal
glycogen in numerous tissues, most notably
in cardiac and skeletal muscle.
www.google.com
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The lysosomal α-1,4-glucosidase was found to be
active at pH 4. However, its activity is not present in
the liver, heart and skeletal muscles of children with
pompe’s disease.
Although the lysosomal α-1,4-glucosidase is often
referred to as maltase, the enzyme is known to have a
broader specificity in that it acts also on the outer chains
of glycogen.
www.google.com
Symptoms
 Type II, usually found in Lapland dogs, is
characterized by vomiting, progressive muscle
weakness, and cardiac abnormalities. Death
usually occurs before two years of age.
Causes
 Type II from a deficiency of acid glucosidase.
Other animals
 Acid maltase-deficient Japanese quails
 Australian cattle
GLYCOGEN STORAGE
DISEASES (GSD) TYPE
III ?

known as Forbes-Cori disease or limit dextrinosis
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Due to inability to produce enough glycogen
debranching enzyme ( GDE )
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The gene responsible for making (GDE)
(Glucosyl Transferase & ɑ-1,6-Glucosidae) is the AGL
gene
Normal Glycogen Debranching
 First, phosphorylase removes 7 glucose molecules (7 black circles from the
unbranched outer part of glycogen molecule) from the other glucose molecules
in a glycogen molecule until only 4 glucosyl units (3 green circles and the 1 red
circle) remain before an alpha1,6 branch point .
 The transferase debranching enzyme then transfers the 3 (green) glucose
residues from the short branch to the end of an adjacent branch of the glycogen
molecule
 The glucosidase debranching enzyme then removes the glucose molecule(the
red circle) remaining at the alpha1,6 branch point.
Abnormal Glycogen Debranching
 Mutation of AGL gene = reduce GDE production = GSD III = Incomplete
debranching of glycogen = Less glucose released , Glycogen stored as limit
dextrin structure
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If one copy of the AGL gene is altered but the
second copy is not, then the body can follow the
instructions on the second copy in order to produce
enough debranching enzyme. When both copies of
an individual’s AGL gene are altered, the body is
unable to read any instructions on how to make the
proper amount of debranching enzyme. As a result,
the individual has GSD III.
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GSD IIIa - includes muscle and liver involvement
GSD IIIb - liver involvement but no muscle involvement
GSDIIIc (extremely rare) - Presumably the result of
deficiency of only glucosidase debranching activity
GSDIIId (extremely rare)- Presumably the result of
deficiency of only transferase debranching activity
GLYCOGEN STORAGE
DISEASES (GSD) IV and
V?
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GSD type IV, also known as amylopectinosis
or Andersen disease, is a rare disease that
leads to early death.
In 1956, Andersen reported the first patient
with progressive hepatosplenomegaly and
accumulation of abnormal polysaccharides.
The main clinical features are liver
insufficiency and abnormalities of the heart
and nervous system.
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Type IV, or Andersen's disease, is caused by glycogen
branches enzyme deficiency in the liver, brain, heart,
skeletal muscles, and skin fibroblasts.
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The glycogen constructed in GSD IV is abnormal and
insoluble. As it accumulates in the cells, cell death
leads to organ damage.
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Infants born with GSD IV appear normal at birth, but
are diagnosed with enlarged livers and failure to thrive
within their first year.
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Infants who survive beyond their first birthday
develop cirrhosis of the liver by age 3-5 and die as a
result of chronic liver failure.
 Symptoms
and sings:
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1.The liver (cirrhosis) progressive and
spleen enlarge.
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2. Death typically occurs by five years of
age.
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GSD type V, also known as McArdle disease,
affects the skeletal muscles.
Initial signs of the disease usually develop in
adolescents or adults.
Muscle phosphorylase deficiency adversely
affecting the glycolytic pathway in skeletal
musculature causes GSD type V. Like other
forms of GSD, McArdle disease is
heterogeneous.

Caused by glycogen phosphorylase deficiency in
skeletal muscles.
 The phosphorylase enzyme plays a vital role in
the breakdown of glycogen into glucose.
 glucose can not be released from the glycogen
stored in skeletal muscles to create energy.
 People with type V GSD experience problems
performing and completing most exercises,
especially anaerobic exercises.
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muscle weakness and cramping brought on
by exercise, as well as burgundy-colored
urine after exercise due to myoglobin (a
breakdown product of muscle) in the urine.