Glycogen Storage DiseasesMSC BT III-13006

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.

The liver glycogenoses

GSD I GSD III GSD IV GSD VI GSD IX GSD 0.

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