Glucokinase mutations in young children with hyperglycemia.
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 hyperglycemia without evidence for autoimmune destruction of beta-cells.


METHODS
We genetically analyzed four families of young children with fasting hyperglycemia with family histories of diabetes for mutations in the genes for hepatocyte nuclear factor 4 alpha (HNF4alpha), glucokinase (GCK), and hepatocyte nuclear factor 1 alpha (HNF1alpha), the genes responsible for MODY1, 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 hyperglycemia without ketosis with family histories of diabetes can provide important prognostic information to guide therapy and exclude preclinical type 1 diabetes mellitus.
Codner
Ethel
E
Institute of Maternal and Child Research (I.D.I.M.I.), School of Medicine, University of Chile, Santiago, Chile. ecodner@med.uchile.cl
Deng
Liyong
L
Pérez-Bravo
Francisco
F
Román
Rossana
R
Lanzano
Patricia
P
Cassorla
Fernando
F
Chung
Wendy K
WK
D001483:Base Sequence; D001724:Birth Weight; D001786:Blood Glucose / Q000378:metabolism; D002648:Child; D017931:DNA Primers; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005941:Glucokinase / Q000235:genetics*; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics; D006801:Humans; D006943:Hyperglycemia / Q000201:enzymology* / Q000235:genetics*; D008297:Male; D009154:Mutation; D010375:Pedigree
D001786:Blood Glucose; D017931:DNA Primers; C496592:HNF4A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D051557:Hepatocyte Nuclear Factor 4; D005941:Glucokinase