Molecular genetics of type 1 glycogen storage disease

Glycogen storage disease type 1 (GSD 1) comprisesa group of autosomal reces sive inherited metabolic disorders caused by deficiency of the microsomal m ulticomponent glucose-6-phosphatase system. Of the two known transmembrane proteins of the system, malfunction of the catalytic subunit (G6Pase) chara cterizes GSD 1a, GSD 1 non-a is characterized by defective microsomal gluco se-g-phosphate or pyrophosphate/phosphate transport due to mutations in G6P T (glucose-6-phosphate translocase gene) encoding a microsomal transporter protein. Mutations in G6Pase and G6PT account for similar to 80 and similar to 20% of GSD 1 cases, respectively. G6Pase and G6PT work in concert to ma intain glucose homeostasis in gluconeogenic organs, Whereas G6Pase is exclu sively expressed in gluconeogenic cells, G6PT is ubiquitously expressed and its deficiency generally causes a more severe phenotype. Rapid confirmatio n of clinically suspected diagnosis of GSD 1, reliable carrier testing, and prenatal diagnosis are facilitated by mutation analyses of the chromosome 11-bound G6PT gene as well as the chromosome 17-bound G6Pase gene. (C) 2001 Academic Press.