Glycogen Storage DiseaseMechanisms
Amandeep Kaur Dhaliwal, Navneet Madhar, Onella Pereira and Superna RameshOctober 6th, 2015
PHM142 Fall 2015 Instructor: Dr. Jeffrey Henderson
Overview
1. Introduction to Glycogen Storage Disease
2. Type 4: Transglucosidase Deficiency
3. McArdie’s Disease
4. von Gierke Disease
5. Tarui Disease
6. Disease Management
7. Summary
Glycogen Storage Disease (GSD)
● Inability for the body to break down glycogen to free glucose
● Type I-VII and Type O
● Affects all organs, namely liver, kidneys and muscle
Glycogen Synthesis
•Glycogen branches are formed by the branching enzyme
amylo-(1,4→1,6)-transglycosylase
• Transfer of 6- or 7-residues to chain ≥ 11 residues
• Polymer adds additional non-reducing end for
glycogen synthase
Type IV
• Deficiency of enzyme
-Normal amount of glycogen
-Longer outer branches
-Impact on storage reserve
GSD Mechanism : McArdie’s Disease
GSD Mechanism : von Gierke’s Disease
GSD Mechanism: Tarui Disease
● Enzyme deficiency decreases the rate of conversion of fructose-6-phosphate to fructose-1,6-bisphosphate
● Slows breakdown of glycogen○ Prevents normal breakdown of
glucose○ Accumulation of glycogen in
muscles○ Lack of fuel sources for
muscles
Disease Management
● No specific treatment
● Diet therapy beneficial in certain cases
● High protein diet to increase muscle function in patients with muscle weakness or exercise intolerance
● Monitor glucose levels
● Rest, in some cases
Summary: Glycogen Storage Diseases
Target Gene Enzyme Affected
Type I G6PC and SLC37A4
Glucose-6-phosphatase Glucose-6-translocase
Type IV GBE1 Amylo α1,4 - α1,6- transglucosidase
Type V PYGM Myophosphorylase
Type VII PFKM Phosphofructokinase
● Management: Monitoring lifestyle (exercise and glucose)● All diseases result in an increase in glycogen
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“Glycogen storage disease type IV.” Genetics Home Reference. 2015. U.S. National Library of Medicine. Accessed Sept 17, 2015 <http://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-iv#diagnosis>McArdle Syndrome.”
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R.H. Garret, C.M. Grisham, S. Andreopoulos, Willmore and I.E. Gallouzi, Biochemistry, First Canadian Edition, Nelson (2013);
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