Inactivation of the glucose 6-phosphate transporter causes glycogen storage disease type 1b

Glycogen storage disease type 1b (GSD-1b) is proposed to be caused by a def iciency in microsomal glucose 6-phosphate (G6P) transport, causing a loss o f glucose-6-phosphatase activity and glucose homeostasis, However, for deca des, this disorder has defied molecular characterization. In this study, we characterize the structural organization of the G6P transporter gene and i dentify mutations in the gene that segregate with the GSD-1b disorder. We r eport the functional characterization of the recombinant G6P transporter an d demonstrate that mutations uncovered in GSD-1b patients disrupt G6P trans port. Our results, for the first time, define a molecular basis for functio nal deficiency in GSD-1b and raise the possibility that the defective G6P t ransporter contributes to neutropenia and neutrophil/monocyte dysfunctions characteristic of GSD-1b patients.