What is Glycogen Storage Disease Type Ia?

Glycogen storage disease type Ia (GSDIa) is a genetic disorder characterized by accumulation of glycogen in organs and tissues, impairing their normal function. This can lead to organ damage and other complications if left untreated. There are two types glycogen storage disease: GSDIa and GSDIb. GSDIa and GSDIb are caused by different mutations and have different symptoms. The age of onset of GSDIa is typically 3-4 months of age. Common symptoms include hypoglycemia (low levels of sugar in blood), lactic acidosis (lactic acid buildup), hyperuricemia (high blood levels of uric acid) and hyperlipidemia (excessive fat in blood). Individuals affected with GSDIa can develop thin extremities, short stature and enlarged liver over time. GSDIa is caused by mutations in the G6PC gene, which encodes the glucose-6-phosphatase enzyme. Glucose-6-phosphatase (G6Pase) is normally involved in the breakdown of glucose-6-phosphate (G6P) to glucose, the main energy supply for cells in the body. At least 85 mutations in the G6PC gene have been identified which cause GSDIa. Mutations in the G6PC gene can inhibit the activity of the G6Pase. Two specific mutations are of particular interest for people with Ashkenazi Jewish descent, R83C and Q347X. Both of these mutations result in inactivation of the G6PC enzyme. Without this enzyme, glucose-6-phosphate cannot be broken down properly, resulting in its conversion to glycogen and fat for storage. Excessive accumulation of glycogen and fat in cells is toxic and eventually leads to organ and tissue damage throughout the body. References: Bali DS, Chen YT, Goldstein JL (2006) [Updated 2013 Sep 19]. Glycogen Storage Disease Type I. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016. Chou JY, Mansfield BC (2008). Mutations in the Glucose-6-Phosphatase-α (G6PC) Gene that Cause Type Ia Glycogen Storage Disease. Human mutation. 29(7): 921-930. Jose CP, Ferreira MD, Schreiber-Agus N, Carter SM, Klugman S, MDa, Gregg AR, Gross SJ (2014). Carrier testing for Ashkenazi Jewish disorders in the prenatal setting: navigating the genetic maze. American Journal of Obstetrics and Gynecology. 211(3): 197-204.
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