Background

Glycogen storage disease type Ib (GSD-Ib) is an autosomal recessive disorder caused by deficiencies in glucose-6-phosphate transporter (G6PT), a ubiquitously expressed endoplasmic reticulum (ER) protein that translocates G6P from the cytoplasm into the ER lumen. Inside the ER, G6P is hydrolyzed to glucose and phosphate by either the liver/kidney/intestine-restricted glucose-6-phosphatase-α (G6Pase-α or G6PC) or the ubiquitously expressed G6Pase-β. G6PT and G6Pase are functionally co-dependent and form the G6PT/G6Pase complexes. The G6PT/G6Pase-α complex maintains interprandial blood glucose homeostasis, while the G6PT/G6Pase-β complex maintains neutrophil/macrophage homeostasis and function. Therefore, GSD-Ib is not only a metabolic – but also an immune disorder – characterized by impaired glucose homeostasis, neutropenia, and myeloid dysfunction.

Allowing GSD-Ib to go untreated in juveniles can lead to