1. Glycogen Storage Disease
Brandon Ng, Hajun Chon, Jagjit Flora
Nov 19, 2019
PHM142 Fall 2019
Coordinator: Jeffrey Henderson

2. Background Info What is GSD?
Condition affecting glycogen storage and/or synthesis
Types of GSD
Grouped by which enzyme is missing
Hereditary Condition
Caused by various mutations in genes
Autosomal recessive pattern
GSD Type 1 (GSD1) or von Gierke Disease

3. Mechanism Type 1A Mutation in the G6PC gene
Defect in Glucose-6-Phosphatase
Cannot convert glucose-6-phosphate to glucose
Type 1B
Mutation in the SLC37A4 gene
Defect in the Glucose-6-Phosphate Transporter I
Cannot transport glucose-6-phosphate from the cytosol to the endoplasmic reticulum

4. Healthy Individual

5. Type 1A and 1B

6. 1B 1A

7. So What Happens? Glucose-6-Phosphate Pyruvate Lactic Acid Production
Acetyl-CoA 🡪 Fatty Acids and Cholesterol
Ribose-5-Phosphate
Nucleic acid synthesis
Decrease in Glucose

8. Symptoms for Type 1A About 80% have these symptoms
Deficiency of G6Pase due to mutation in G6Pc gene
Full cheeks
Hyperlipidemia
Low blood sugar levels
High blood uric acid levels
Shorter height

9. Symptoms for Type 1B Mutation in SLC37A4 gene Autosomal recessive
Enlarged kidney
Enlarged liver
Hypoglycemia
Hyperlipidemia
Neutropenia
Delayed puberty

10. Diagnosis
Blood test
Ultrasound
Tissue Biopsy
Gene testing

11. Treatments - GSD1 Glycosade - XR Supplementation (i.e. vitamins)
Genetic disorder - treat the symptoms
Dietary restrictions
Maintain blood glucose levels - Restrictive schedule
Continuous gastric tube feeds
Uncooked cornstarch
Glycosade - XR
Supplementation (i.e. vitamins)
No intake of galactose, sucrose, fructose
Hepatomegaly
Metabolic derangements

12. Treatments - Continued
Medications
Allopurinol - uric acid
HMG CoA reductase inhibitor - lipidemia
GCSF - Neutropenia
Given with Vit. E
Liver Transplant

13. Novel Treatment Gene Therapy
Early Clinical Trials: UCONN Health (2018) - 1A
Enzyme replacement via adeno-associated virus (AAV)
Positive Results - 1 year span (2019)

14. Summary GSD is a hereditary disease that affects glycogen storage.
There are different types such as Type 1a and Type 1b.
Type 1a
Mutation in G6PC gene
Type 1b
Mutation in SLC37A4 gene
Results in enlarged kidneys and liver.
Treatments are based on treating the symptoms (dietary restrictions and supplements)
New treatment based on gene therapy

15. References
Chen, M. A., & Weinstein, D. A. (2016). Glycogen storage diseases: Diagnosis, treatment and outcome. Translational Science of Rare Diseases, 1(1), 45–72. doi: /trd
Chou, J. Y., Jun, H. S., & Mansfield, B. C. (2010). Glycogen storage disease type I and G6Pase-β deficiency: etiology and therapy. Nature reviews. Endocrinology, 6(12), 676–688. doi: /nrendo
Glycogen Storage Disease. (n.d.). Retrieved from
Glycogen storage disease type I - Genetics Home Reference - NIH. (n.d.). Retrieved from
Hiraiwa, H., Pan, C.-J., Lin, B., Moses, S. W., & Chou, J. Y. (1999). Inactivation of the Glucose 6-Phosphate Transporter Causes Glycogen Storage Disease Type 1b. Journal of Biological Chemistry, 274(9), 5532–5536. doi: /jbc
Kishnani, P. S., Sun, B., & Koeberl, D. D. (2019). Gene therapy for glycogen storage diseases. Human Molecular Genetics, 28(R1), R31–R41.
Woods, L. (2018, July 27). First patient receives novel gene therapy for GSD. Retrieved from
Glycogen storage disease type 1B. (n.d.). Retrieved from
Glycogen Storage Disease (GSD) Diagnosis and Tests. (n.d.). Retrieved from
Glycogen Storage Disease Type 1a