THE GENE FOR GLYCOGEN-STORAGE-DISEASE TYPE 1B MAPS TO CHROMOSOME 11Q23

Glycogen-storage disease type 1 (GSD-1), also known as ''von Gierke di sease,'' is caused by a deficiency in microsomal glucose-6-phosphatase (G6Pase) activity. There are four distinct subgroups of this autosoma l recessive disorder: 1a, 1b, 1c, and 1d. All share the same clinical manifestations, which are caused by abnormalities in the metabolism of glucose-6-phosphate (G6P). However, only GSD-1b patients suffer infec tious complications, which are due to both the heritable neutropenia a nd the functional deficiencies of neutrophils and monocytes. Whereas G 6Pase deficiency in GSD-1a patients arises from mutations in the G6Pas e gene, this gene is normal in GSD-1b patients, indicating a separate locus for the disorder in the 1b subgroup. We now report the linkage o f the GSD-1b locus to genetic markers spanning a 3-cM region on chromo some 11q23. Eventual molecular characterization of this disease will p rovide new insights into the genetic bases of G6P metabolism and neutr ophil-monocyte dysfunction.