Glycogen is the stored form of glucose which serves as a buffer for glucose needs. It is formed in periods of dietary carbohydrate loading and broken down when glucose demand is high or dietary availability is low. The main role of glycogen in the liver is to store glucose for release to tissues that are unable to synthesize significant amounts during fasting. In the muscle, glycogen serves as the primary source of energy for high-intensity muscle activity by providing substrates for the generation of adenosine triphosphate. Glycogen storage diseases (GSD) are rare inborn errors of glycogen metabolism that result from mutations in genes involved in glycogen storage. The age of onset varies from in utero to adulthood. The most affected organs are the liver and muscle where glycogen is abundant. Liver manifestations include hypoglycemia and hepatomegaly while muscle manifestations include cramps, exercise intolerance, easy fatigability, and progressive weakness. GSD III is due to an abnormality in the Amylo-Alpha-1, 6-Glucosidase, 4-Alpha-Glucanotransferase (AGL) gene causing deficiency of the glycogen debrancher enzyme. It is inherited as an autosomal recessive trait. Estimated prevalence is 1:100,000. It is characterized by variable liver, cardiac muscle and skeletal involvement. GSD IIIa is present in about 85% of affected individuals and manifests with liver and muscle involvement. GSD IIIb is in about 15 % of affected individuals with liver involvement only. The patient was born to a 35-year-old African American mother at 38 weeks gestation. Labor and delivery were uncomplicated. Initial labs showed blood glucose of 38 mg/dl for which he was placed on a hypoglycemia protocol. Breastfeeding was started successfully with no more noted hypoglycemia and he was discharged home. At 11 months he was taken to the ER after a witnessed tonic clinic seizure. Blood glucose was noted to be 24 mg/dl. He was managed with hypoglycemia protocol and Pediatric Endocrinology team consulted. Labs showed elevated liver enzymes, creatinine kinase and cholesterol with ALP 1101 units/L, AST 1822 units/L, ALT 1148 units/L, CK 783 units/L, total cholesterol 223mg/dl, triglyceride 249 mg/dl and HDL 30 mg/dl. Abdominal US showed hepatomegaly and echo showed left ventricular and septal hypertrophy. GSD was suspected so genetic testing was done and showed 2 frameshift mutations in the AGL gene confirming GSD Type IIIa. He was started on a low carbohydrate high protein diet together with corn starch with minimal hypoglycemia episodes. He has been closely followed at the pediatric Endocrinology clinic and is now 17 years old. He has a DEXCOM continuous glucose monitor. Most recent labs show some improvement in liver enzymes and lipids. Both of his parents are positive for the GSD III trait. Unexplained hypoglycemia warrants a thorough work up as highlighted in this case. Most of the severe forms of GSDs are diagnosed in childhood but some mild forms can be diagnosed in adulthood. Both pediatric and adult endocrinologists should have sufficient knowledge on the diagnosis and management of GSDs.
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