Understanding glycogen storage disease type Ia (GSDIa)

GSDIa is a rare metabolic disorder that leads to impaired glucose production¹

Image illustrative of disease types within the larger GSD hierarchy. Not to scale based on disease prevalence.

Glycogen storage disease type Ia (GSDIa, a von Gierke disease) is a metabolic disorder caused by a deficiency in the enzyme glucose-6-phosphatase (G6Pase) due to pathogenic variants of the G6PC (G6PC1) gene.¹ This deficiency leads to an inability to release glucose from stored glycogen or generate glucose endogenously, especially during periods of fasting or high energy demands, leaving patients at risk of severe, life-threatening hypoglycemia.^1,2

Pathophysiology of GSDIa

Unaffected Glucose Production

Glucose is produced endogenously to maintain normal blood glucose levels and is increasingly used during periods of fasting or high energy demands^1,2

G6Pase is a critical enzyme in the production of glucose, as it catalyzes the conversion of G6P to glucose during the final step of both glycogenolysis and gluconeogenesis¹

G6Pase Deficiency in GSDIa

Without functional G6Pase, impaired glycogenolysis and gluconeogenesis result in an inability to release glucose, causing potentially life-threatening episodes of hypoglycemia, especially during periods of fasting or high energy demands^1,2

Excess glycogen builds up in the liver and kidneys, and accumulated G6P is shunted to alternative metabolic pathways, resulting in multisystemic complications¹

Image illustrative of disease types within the larger GSD hierarchy. Not to scale based on disease prevalence.

Consequences of G6Pase Deficiency¹

A deficiency in G6Pase results in impaired glycogenolysis and gluconeogenesis, leading to hypoglycemia, excess hepatic glycogen storage, and the shunting of G6P to alternative metabolic pathways¹

Adapted from Derks et al.¹

GSDIa is an autosomal recessive disease

25% RISK

If both parents are carriers of pathogenic variants of the G6PC (G6PC1) gene, there is a 1 in 4 chance with each pregnancy that they will have a child affected with GSDIa³

Incidence of GSDIa in the US is 0.8 in 100,000 live births

US Incidence of GSDI

1/100,000 live births²

80% of GSDI cases are GSDIa²

Learn about presentation and diagnosis

Abbreviations: G6P, glucose-6-phosphate; G6Pase, glucose-6-phosphatase; GSDIa, glycogen storage disease type Ia; US, United States.

References: 1. Derks TGJ, Rodriguez-Buritica DF, Ahmad A, et al. Glycogen storage disease type Ia: current management options, burden and unmet need. Nutrients. 2021;13(11):3828. 2. Kanungo S, Wells K, Tribett T, El-Gharbawy A. Glycogen metabolism and glycogen storage disorders. Ann Transl Med. 2018;6(24):474. 3. National Organization for Rare Disorders. Glycogen storage disease type I. Accessed July 1, 2025. https://rarediseases.org/rare-diseases/glycogen-storage-disease-type-i/

Understanding GSDIa

GSDIa is a rare metabolic disorder that leads to impaired glucose production1