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 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>

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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/>

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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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