Glucokinase mutations in young children with hyperglycemia

Abstract

Background The etiology of mild hyperglycemia without ketoacidosis in young children is often unknown. Maturity onset diabetes of youth (MODY) is a form of diabetes mellitus (DM) characterized by fasting hyperglycernia without evidence for autoimmune destruction of beta-cells. Methods We genetically analyzed four families of young children with fasting hyperglycernia with family histories of diabetes for mutations in the genes for hepatocyte nuclear factor 4 alpha (HNF4 alpha), glucokinase (GCK), I and hepatocyte nuclear factor 1 alpha (HNFl alpha), the genes responsible for MODYI, MODY2, and MODY3, respectively.

Results We identified mutations in GCK (Gly258Asp, Arg303Trp, and Arg191Gln) in three of the four families. Molecular genetic characterization in these children clarified the etiology and prognosis of the hyperglycemia and allowed discontinuation of insulin therapy in one family.

Conclusions We conclude that molecular evaluation for MODY in children with mild fasting hyperglycernia without ketosis with family histories of diabetes can provide important prognostic information to guide therapy and exclude preclinical type 1 diabetes mellitus.