Glycogen storage disease due to hepatic glycogen synthase deficiency

Glycogen storage disease due to hepatic glycogen synthase deficiency, also known as glycogen storage disease type 0a (GSD 0a) or GSD type 0, is a rare inherited metabolic disorder caused by deficiency of the liver isoform of glycogen synthase, the enzyme responsible for synthesizing glycogen from glucose. It is caused by pathogenic variants in the GYS2 gene located on chromosome 12p12.1. Because the liver cannot properly store glucose as glycogen, affected individuals experience fasting hypoglycemia (low blood sugar after periods without food) and postprandial hyperglycemia and hyperlactatemia (high blood sugar and elevated lactic acid after meals). This metabolic imbalance reflects the liver's inability to buffer blood glucose levels through glycogen storage and release. The disease primarily affects the liver and glucose metabolism. Key clinical features typically present in infancy or early childhood and include fasting ketotic hypoglycemia, which can cause seizures, lethargy, and pallor, particularly in the morning before breakfast or during intercurrent illness. After meals, patients may exhibit hyperglycemia and glycosuria (glucose in the urine) because excess glucose cannot be stored as glycogen. Notably, unlike many other glycogen storage diseases, the liver is usually not enlarged (no hepatomegaly) because glycogen content in the liver is actually reduced rather than accumulated. Some patients may also experience short stature and elevated blood ketone levels during fasting. There is no specific curative treatment for GSD type 0a. Management focuses on dietary strategies to prevent hypoglycemia, including frequent meals, avoidance of prolonged fasting, and consumption of complex carbohydrates (such as uncooked cornstarch) before bedtime to provide a slow release of glucose overnight. A high-protein diet may also be beneficial as amino acids can serve as alternative gluconeogenic substrates. With appropriate dietary management, the prognosis is generally favorable, and symptoms tend to improve with age as patients learn to manage their dietary intake. Early diagnosis and consistent nutritional management are essential to prevent complications from recurrent hypoglycemia.

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