PHM142 Fall 2015
Instructor: Dr. Jeffrey Henderson
Glycogen Storage Disease
Mechanisms
Amandeep Kaur Dhaliwal, Navneet Madhar, Onella Pereira and Superna Ramesh
October 6th, 2015
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-6phosphate to fructose-1,6bisphosphate
● 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 - α1,6transglucosidase
Type V
PYGM
Myophosphorylase
Type VII
PFKM
Phosphofructokinase
● Management: Monitoring lifestyle (exercise and glucose)
● All diseases result in an increase in glycogen
References
“Glycogen Storage Diseases.” Coriell Institute for Medical Research. Accessed Sept 17, 2015
<https://catalog.coriell.org/0/Sections/Collections/NIGMS/gsd_pathway.aspx?PgId=254>“
“Glycogen storage disease type I.” Genetics Home Reference. 2015. U.S. National Library of Medicine. Accessed Sept 17, 2015
<http://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-i>
“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.”
“Glycogen storage disease type V.” Genetics Home Reference. 2015. U.S. National Library of Medicine. Accessed Sept 17, 2015
<http://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-v>
“Glycogen storage disease type VII.” Genetics Home Reference. 2015. U.S. National Library of Medicine. Accessed Sept 17, 2015
<http://ghr.nlm.nih.gov/condition/glycogen-storage-disease-type-vii#diagnosis>
J. Berg., J. Tymoczko. & L. Stryer. “A Biochemical Understanding of Glycogen-Storage Diseases Is Possible.” Biochemistry 5th Ed. H. Freeman and
Company. New York. 2002. Section 21.5.4. Accessed through NCBI <http://www.ncbi.nlm.nih.gov/books/NBK22444/>
Medline Plus. 2015. U.S. National Library of Medicine. Accessed Sept 17, 2015 from <https://www.nlm.nih.gov/medlineplus/ency/article/000329.htm>
R.H. Garret, C.M. Grisham, S. Andreopoulos, Willmore and I.E. Gallouzi, Biochemistry, First Canadian Edition, Nelson (2013);
“Type Ia Glycogen Storage Disease” Medscape. Wayne E Anderson. 2015. Accessed Sept 17, 2015
<http://emedicine.medscape.com/article/119318-overview>