GSD

1. Glycogen Storage
Diseases
MSC BT III-13006

2. Introduction
 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
maintenance of normoglycemia.
 In muscle, glycogen provides energy for muscle contraction.

3. Glycogen storage diseases
 Glycogen storage disease is the result of defects in the processing of
glycogen synthesis or breakdown within muscles, liver, and other cell
types
the GSDs can be divided in three main groups:
those affecting liver,
those affecting muscle,
and those which are generalized.

4. The liver glycogenoses
 GSD I
 GSD III
 GSD IV
 GSD VI
 GSD IX
 GSD 0.

5. GSD l(Von Gierke Disease)
 caused by deficiency of the of glucose-6-
phosphatase (G6Pase)
 people with Type I GSD are able to store glucose
as glycogen but not able to release it normally,
with time the stores of glycogen build up in the
liver causing the liver to swell (hepatomegaly).
Glycogen G1P G6P
G6Pase
Glucose

6.  Symptoms :
 Enlarged liver
 Low blood sugar (during fasting )
 High levels of lactate, fats, and uric acid in the blood
 Impaired growth and delayed puberty
 TREATMENT:-Initially glucose via a nasogastric tube.
 As children get older, glucose is replaced with cornstarch taken
orally

7. GSD lll(Cori disease)
 GSD III is caused by a deficiency of glycogen debrancher enzyme
activity. The normal structure of glycogen has branches. In GSD III,
glycogen is able to be partially broken down to release some
glucose. However, the remaining glycogen that is not completely
broken down has short outer chains and collects in the liver, muscle,
and heart. The build-up of this atypical form of glycogen can cause
damage to tissues.
glycogen debrancher enzyme
Glycogen G1P

8.  Symptoms : Swollen abdomen, low blood sugars on fasting,
growth delayed during childhood.
 Secondary symptoms Problems with muscle weakness.
 Diagnosis:- liver biopsies. Biopsy of the liver shows inflammatory
changes (swollen liver cells) with great elevations of abnormal-
structured glycogen content and a deficiency of the debrancher
enzyme (GDE).
Treatment:-
protein supplements for muscle disorder.

9. GSD lV(Andersen disease)
 GSD IV is caused by a deficiency of glycogen branching enzyme.
The normal structure of glycogen is formed by branches. The
absence of glycogen branching enzyme leads to formation of
glycogen with fewer branch points and longer outer chains than
normal
Abnormally structured glycogen forms.
Glycogen branching enzyme
G1P UDPG Glycogen

10.  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
 Treatment:- No treatment apart from liver transplantation has been
found to prevent progression of the disease. Most children with this
condition die before two years of age.

11. GSD VI(Hers disease)
 GSD VI is one of the least severe forms of GSD
 GSD VI is caused by a deficiency of liver phosphorylase enzyme,
which helps with the breakdown of glycogen to glucose. Due to the
inability to breakdown glycogen to glucose and the resulting
storage of extra glycogen in the live
liver phosphorylase enzyme
Glycogen G1P

12.  Symptoms :-Hepatomegaly
 hypoglycaemia
 growth retardation
 hyperlipidaemia.
 Diagnosis :-blood sugar testing
 Cholesterol testing
 liver function tests may also be seen
Treatment:Need frequent feeding to avoid hypoglycaemia.

13. GSD IX(Phosphorylase Kinase
Deficiency)
 GSD type IX is a disorder in which the body cannot break down
glycogen People with GSD IX are deficient in an enzyme called
phosphorylase kinase (PhK). A deficiency in PhK causes glycogen to
accumulate in various tissues including liver, muscle, red blood cells,
and sometimes in the heart.
 Phosphorylase kinase (PhK) is a specific protein kinase which
activates glycogen phosphorylase to release glucose-1-phosphate
from glycogen.
Phosphorylase Kinase
Glycogen G1P

14.  Symptoms :-People with GSD IX develop enlarged livers and may
have low blood sugar due to inability to breakdown glycogen
 Diagnosis:-
 Blood profiling
 Biopsy of liver
 Treatment:- It can be prevented by maintaining a high
carbohydrate (starchy foods) diet, adequate amounts of protein in
the diet, and avoiding long periods of not eating.

15. GSD 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 hypoglycaemia.
glycogen synthase
G1P UDPG Glycogen
 Symptoms:- Before breakfast drowsiness
 Tiredness
 looking pale
 vomiting.
 Secondary symptoms Quick to tire, muscle cramps

16.  Diagnosis :-
 Blood tests
 Blood glucose: hypoglycaemia is likely
 Liver function tests: monitoring for hepatic failure
 Treatment :-
 cornstarch to reduce overnight hypoglycemia.

18. GSD Type Enzyme
Deficiency
Symptoms Diagnosis Treatment
Type l G6PTase Hepatomegaly
Low blood sugar
Impaired growth
Liver biopsy cornstarch taken orally
Type lll Debranching
Enzyme
Swollen abdomen
Tissue damage
Muscle weakness
Liver biopsy
abnormal-
structured glycogen
protein supplements for
muscle disorder
Type lV Branching
Enzyme
Growth delay in
childhood
Enlarged liver
abnormal-
structured glycogen
with long outer
chain
liver transplantation
Type Vl Liver
phosphorylase
Hepatomegaly
hypoglycaemia
growth retardation
hyperlipidaemia.
blood sugar testing
Cholesterol
testing
liver function
Need frequent feeding
to avoid
hypoglycaemia.
Type lX Phosphorylase
Kinase
enlarged livers and
may have low blood
sugar
Blood profiling
Biopsy of liver
Prevent by taking high
carbohydrate diet
Type 0 Glycogen Tiredness Blood tests cornstarch to reduce

19.  References:-
 http://www.agsd.org.uk/tabid/1324/default.aspx 12-10-2014 21:48
 http://www.dukechildrens.org/services/medical_genetics/glycogen
_storage_disease types 12-10-2014 21:48
 http://www.agsdus.org/html/glycogenandgsds.html
12-10-2014 21:48
 http://image.slidesharecdn.com/glycogenstoragediseasegsd-
110505030652-phpapp01/95/glycogen-storage-disease-gsd-4-
728.jpg?cb=1304582937 12-10-2014 21:48