2. Glycogen :
Glycogen, an important energy source, is
found in most tissues, but is especially
abundant in liver and muscle.
In the liver, glycogen serves as a glucose
reserve for the maintenanceof
normoglycemia.
In muscle, glycogen provides energy for
muscle contraction.
the need to store or release
glucose is primarily signaled
by the hormones insulin and
glucagon.
3. There are about eleven known types of GSD,
which are classified by a number, by the
name of the defective enzyme, or by the
name of the doctor who first described the
condition
the GSDs can be divided in three main
those affecting liver, groups:
those affecting muscle,
and those which are generalized.
4. Note :
All types of GSD cause the body to either not
be able to make enough glucose, or not be
able to use glucose as a form of energy.
Determining what type of GSD a person has
(diagnosis) depends on an individual's
symptoms. Typically a doctor will do a
physical examination and some blood and
urine testing. Occasionally, a muscle and/or
liver biopsy will be needed to measure the
amount of a certain enzyme in that part of the
body.
5. A. The liver glycogenoses :
The liver GSDs comprise
GSD I, GSD III, GSD IV, GSD VI, the liver
forms of GSD IX, and
GSD 0.
6. Type I - Von Gierke Disease:
Comprises
GSD Ia: caused by deficiency of the catalytic
subunit of glucose-6-phosphatase (G6Pase),
GSD Ib: due to deficiency of the endoplasmic
reticulum (ER) glucose-6-phosphate (G6P)
translocase.
7.
8. Symptoms :
Enlarged liver and kidneys
Low blood sugar
High levels of lactate, fats, and uric acid in
the blood
Impaired growth and delayed puberty
Bone thinning from osteoporosis
Increased mouth ulcers and infection
9. Metabolic disorder :
G6Pase is unique since its catalytic site is
situated inside the lumen of the ER
Hypoglycemia: occurs during fasting as soon as
exogenous sources of glucose are exhausted,
since the final steps in both glycogenolysis and
gluconeogenesis are blocked.
Hyperlactatemia: is a consequence of excess
G6P that cannot be hydrolysed to glucose and
is further metabolised in the glycolytic pathway,
ultimately generating pyruvate and lactate.
10.
11.
12. Glycogen Storage Disease Type III
(Debranching Enzyme Deficiency):
. GSD III, also known as Cori or Forbes
disease, is an autosomal recessive
disorder due to deficiency of GDE which
causes storage of glycogen with an
abnormally compact structure, known as
phosphorylase limit dextrin
13.
14. Symptoms :
Swollen abdomen due to an enlarged liver
Growth delay during childhood
Low blood sugar
Elevated fat levels in blood
Possible muscle weakness
15. Glycogen Storage Disease Type IV
(Branching Enzyme Deficiency):
Andersen Disease, is an autosomal
recessive disorder due to a deficiency of
glycogen branching enzyme (GBE).
Deficiency of GBE results in the formation
of an amylopectin-like compact glycogen
molecule with fewer branching points and
longer outer chains.
16. Symptoms :
Growth delay in childhood
Enlarged liver
Progressive cirrhosis of the liver (which may
lead to liver failure)
May affect muscles and heart in late-onset
type
17. Glycogen Storage Disease Type 0
( Glycogen Synthase Deficiency)
GSD 0 is caused by a deficiency of glycogen
synthase (GS), a key-enzyme of glycogen
synthesis. Consequently, patients with GS
deficiency have decreased liver glycogen
concentration, resulting in fasting
hypoglycemia.
18.
19. The Muscle Glycogenoses
Glycogen Storage Disease Type V
(Myophosphorylase Deficiency)
Under normal circumstances, muscles cells rely
on oxidation of fatty acids during rest or light
activity. More demanding activity requires that
they draw on their glycogen stockpile.
There are three isoforms of glycogen
phosphorylase:
brain/heart, liver, and muscle, all encoded by
different
genes. GSD V is caused by deficient
21. Glycogen Storage Disease Type
VII(Phosphofructokinase Deficiency)
first described by Tarui
Although glucose may be available as a fuel
in muscles, the cells cannot metabolize it.
Symptoms :
Muscle cramps with exercise
Anemia
22.
23. The Generalized Glycogenoses and
Related Disorders
Type II (Acid Maltase Deficiency)
GSD II is a lysosomal storage disorder,
caused by the generalized deficiency of
the lysosomal enzyme, acid maltase or α-
glucosidase.
Although the defect involves a single
ubiquitous enzyme, it manifests as three
different clinical phenotypes: Infantile,
juvenile, and adult
24. In the infantile form, infants seem normal at
birth, but within a few months they develop
muscle weakness, trouble breathing, and an
enlarged heart. Cardiac failure and death
usually occur before age 2, despite medical
treatment.
The juvenile and adult forms of GSD II affect
mainly the skeletal muscles in the body's
limbs and torso. Decreased muscle strength
and weakness developed
25. Metabolic disorder :
The enzyme defect results in the accumulation
of glycogen within the lysosomes of all
tissues, but particularly in muscle and heart,
resulting in muscle weakness. Serum levels
of transaminases (ASAT, ALAT), CK and CK-
myocardial band (in the infantile form) are
elevated
26.
27. Diagnosis
Muscle biopsy shows a severe vacuolar
myopathy with accumulation of both
intralysosomal and free glycogen in
both the infantile and childhood
variants
28. Treatment :
Enzyme replacement therapy using
recombinant human α-glucosidase,
obtained in large quantities from rabbit milk
has been used successfully;
Four infants with Pompe disease were
treated with spectacular results: although
one patient died of an intercurrent infection
at 4 years of age, all four patients showed
remarkable clinical improvement in motor
and cardiac function and parallel
improvement in muscle morphology.
29. The same therapeutic approach was applied
with success in three children with the
muscular variant Before starting enzyme
replacement, all three were wheelchair-
bound and two were respirator-dependent.
After 3 years of treatment, their pulmonary
function had stabilised and their exercise
tolerance had improved, and the youngest
patient resumed walking independently.
30. Danon Disease
Danon Disease or GSD IIb, or pseudo-
Pompe disease, is an X-linked dominant
lysosomal storage disease due to
deficiency of LAMP-2 (lysosomal-
associated membrane protein 2). The
disease starts after the first decade, is
extremely rare and affects cardiac and
skeletal muscle. Acid maltase activity is
normal, muscle biopsy shows vacuolar
myopathy with vacuoles containing
glycogen and cytoplasmatic degradation
products
