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.
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.
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
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
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
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.
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
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.
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
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.
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
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.
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
Diagnosis :-
Blood tests
Blood glucose: hypoglycaemia is likely
Liver function tests: monitoring for hepatic failure
Treatment :-
cornstarch to reduce overnight hypoglycemia.
GSD Type EnzymeDeficiency
Symptoms Diagnosis Treatment
Type l G6PTase HepatomegalyLow blood sugar Impaired growth
Liver biopsy cornstarch taken orally
Type lll DebranchingEnzyme
Swollen abdomenTissue damageMuscle weakness
Liver biopsyabnormal-structured glycogen
protein supplements for muscle disorder
Type lV BranchingEnzyme
Growth delay in childhood Enlarged liver
abnormal-structured glycogen with long outer chain
liver transplantation
Type Vl Liver phosphorylase
Hepatomegaly hypoglycaemiagrowth retardation hyperlipidaemia.
blood sugar testingCholesteroltestingliver function
Need frequent feeding to avoid hypoglycaemia.
Type lX PhosphorylaseKinase
enlarged livers and may have low blood sugar
Blood profilingBiopsy of liver
Prevent by taking high carbohydrate diet
Type 0 Glycogen synthase
Tirednesslooking palevomiting
Blood testsBlood glucoseLiver function tests
cornstarch to reduce overnight hypoglycemia.
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