Glycogen storage diseases

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.

17. 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 synthase Tiredness looking pale vomiting Blood tests Blood glucose Liver function tests cornstarch to reduce overnight hypoglycemia .

18. 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