Glycogen Storage Disease Mechanisms Amandeep Kaur Dhaliwal, Navneet Madhar, Onella Pereira and...
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Transcript of Glycogen Storage Disease Mechanisms Amandeep Kaur Dhaliwal, Navneet Madhar, Onella Pereira and...
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
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>