Glycogen Synthase Deficiency
Glycogen Storage Disease Type 0
Glycogen Synthase; responsible for catalysing the conversion of glucose to glycogen.
Deficiency results in low to none glycogen stores in the liver; called Glycogen Storage Disease Type 0 (Weinstein, Correia, Saunders, & Wolfsdorf, 2006).
Aetiology
- GYS2 gene, located on chromosome 12p12.1
- 17 different mutations (Correia, Weinstein, & Wolfsdorf, 2009)
- Only 20 reported cases in literature; potentially under-diagnosed (Spiegel, Mahamid, Orho-Meleander, Miron, & Horovitz, 2007).
- Autosomal recessive (Weinstein, Correia, Saunders, & Wolfsdorf, 2006).
(Correia, Weinstein, & Wolfsdorf, 2009)
Metabolic Pathway
Metabolic Pathway
- Anabolic, endergonic reaction
- Generally activated post-prandially
(Berg, Tymoczko, & Stryer, 2002)
Diagnosis
(Journal of Microbiology & Diagnosis, 2017)
Diagnosis
- Liver biopsy used to be the only option
- Mutation analysis of DNA can now be performed with the discovery of GYS2 gene, and is becoming the gold standard
- Initial screening includes monitoring of blood glucose, urine ketones and serum lactate levels
(Weinstein, Correia, Saunders, & Wolfsdorf, 2006).
Symptoms
During fasting, glycogenolysis is not possible due to decreased glycogen stores (Kasapkara et al., 2017)
Symptoms
After consuming carbohydrates, excess glucose is converted to lactate rather than stored as glycogen (Weinstein, Correia, Saunders & Wolfsdorf, 2006).
Untreated
Lack of glucose for energy forces body into ketosis and then eventually hyperketonemia (Lefevre & Aronson, 2000).
Hypoglycaemia, lactic acidosis and hyperketonemia all contribute to short stature and osteopenia (Weinstein, Correia, Saunders & Wolfsdorf, 2006)
Hypoglycaemia, lactic acidosis and hyperketonemia all contribute to sho...
(One Body Osteopathy, 2017)
Treatment
Frequent meal consumption (2-4 hours)
- High protein
- Low GI carbohydrates
- Raw corn starch
(Kasapkara et al., 2017).
Treatment
(Nutrition Station, 2016)
References
- Berg, J. M., Tymoczko, J. L., & Stryer, L. (2002). Biochemistry (5th ed.). New York: W H Freeman.
- Correia, C. E., Weinstein, D. A., & Wolfsdorf, J. I. (2009). Glycogen synthase deficiency. In F. Lang (Ed). Encyclopedia of molecular mechanisms of disease. Retrieved from https://link-springer-com.ez.library.latrobe.edu.au/content/pdf/10.1007%2F978-3-540-29676-8_714.pdf
- ExploreIM. (2017). Achieving health and balance through the art of eating. Retrieved from https://exploreim.ucla.edu/nutrition/achieving-balance-through-the-art-of-eating-demystifying-eastern-nutrition-and-blending-it-with-western-nutrition/
- Jentjens, R., & Jeukendrup, A. E. (2003). Determinants of post-exercise glycogen synthesis during short-term recovery. Sports Medicine, 33(2), 117-144. Retrieved from https://link.springer.com/article/10.2165%2F00007256-200333020-00004#citeas
- Kanikarla-Marie, P., & Jain, S. (2016). Hyperketonemia and ketosis increase the risk of complications in type 1 diabetes. Free Radical Biology And Medicine, 95, 268-277. http://dx.doi.org/10.1016/j.freeradbiomed.2016.03.020
- Kasapkara, Ç., Aycan, Z., Açoğlu, E., Senel, S., Oguz, M., & Ceylaner, S. (2017). The variable clinical phenotype of three patients with hepatic glycogen synthase deficiency. Journal Of Pediatric Endocrinology And Metabolism, 30(4). http://dx.doi.org/10.1515/jpem-2016-0317
- Lefevre, F., & Aronson, N. (2000). Ketogenic Diet for the Treatment of Refractory Epilepsy in Children: A Systematic Review of Efficacy. PEDIATRICS, 105(4), e46-e46. http://dx.doi.org/10.1542/peds.105.4.e46
- McGarry, J., & Foster, D. (1980). Regulation of Hepatic Fatty Acid Oxidation and Ketone Body Production. Annual Review Of Biochemistry, 49(1), 395-420. http://dx.doi.org/10.1146/annurev.bi.49.070180.002143
- National Institute of Health. (2016). What people with diabetes need to know about osteoporosis. Retrieved from https://www.bones.nih.gov/health-info/bone/osteoporosis/conditions-behaviors/diabetes#c
- Nature. (2014). Growth and developme...
- Nature. (2014). Growth and development: bone dysplasia – a frequent cause of short stature in children. Retrieved from http://www.nature.com/nrendo/journal/v10/n6/full/nrendo.2014.49.html?foxtrotcallback=true
- Nutrition Station. (2016). The importance of including protein in your diet. Retrieved from https://nutritionstation.com/importance-including-protein-diet/
- One Body Osteopathy. (2017). Bone health – What is it? And how do I know if I’m at risk. Retrieved from http://onebodyosteo.com.au/bone-health-what-is-it-and-how-do-i-know-if-i-am-at-risk/
- Orho, M., Bosshard, N., Buist, N., Gitzelmann, R., Aynsley-Green, A., & Blümel, P. et al. (1998). Mutations in the liver glycogen synthase gene in children with hypoglycemia due to glycogen storage disease type 0. Journal Of Clinical Investigation, 102(3), 507-515. http://dx.doi.org/10.1172/jci2890
- Özen, H. (2007). Glycogen storage diseases: New perspectives. World Journal Of Gastroenterology, 13(17), 2541. http://dx.doi.org/10.3748/wjg.v13.i18.2541
- Protein Power. (2008). Low-carbers beware the brethalyzers. Retrieved from https://proteinpower.com/drmike/2007/05/21/low-carbers-beware-the-breathalyzer/
- Spiegel, R., Mahamid, J., Orho-Melander, M., Miron, D., & Horovitz, Y. (2007). The variable clinical phenotype of liver glycogen synthase deficiency. Journal of Pediatric Endocrinology & Metabolism, 20, 1339-1342. Retrieved from https://www-degruyter-com.ez.library.latrobe.edu.au/downloadpdf/j/jpem.2007.20.12/jpem.2007.20.12.1339/jpem.2007.20.12.1339.pdf
- Weinstein, D., Correia, C., Saunders, A., & Wolfsdorf, J. (2006). Hepatic glycogen synthase deficiency: An infrequently recognized cause of ketotic hypoglycemia. Molecular Genetics And Metabolism, 87(4), 284-288. http://dx.doi.org/10.1016/j.ymgme.2005.10.006
- Wikipedia. Glycogen (starch) synthase [Image]. Glycogen Synthase. Retrieved 12 October, 2017, from https://en.wikipedia.org/wiki/Glycogen_synthase
- Wikipedia. [Image]. Glycogenesis. Retrieved 12 October, 2017, from https://en.wikipedia.org/wiki/Glycogenesis