MUTATIONS IN THE GLUCOSE-6-PHOSPHATASE GENE THAT CAUSE GLYCOGEN-STORAGE-DISEASE TYPE-1A

Glycogen storage disease (GSD) type 1a is caused by the deficiency Of D-glucose-6-phosphatase (G6Pase), the key enzyme in glucose homeostasi s. Despite both a high incidence and morbidity, the molecular mechanis ms underlying this deficiency have eluded characterization. In the pre sent study, the molecular and biochemical characterization of the huma n G6Pase complementary DNA, its gene, and the expressed protein, which is indistinguishable from human microsomal G6Pase, are reported. Seve ral mutations in the G6Pase gene of affected individuals that complete ly inactivate the enzyme have been identified. These results establish the molecular basis of this disease and open the way for future gene therapy.