Maturity-Onset Diabetes of the Young in Children With Incidental Hyperglycemia:: A multicenter Italian study of 172 families

OBJECTIVE

To investigate the prevalence of maturity-onset diabetes of the young (MODY) in Italian children with incidental hyperglycemia.

RESEARCH DESIGN AND METHODS

Among 748 subjects age 1–18 years with incidental hyperglycemia, minimal diagnostic criteria for MODY were met by 172 families. Mutational analyses of the glucokinase (GCK) and hepatocyte nuclear factor 1α (HNF1Α) genes were performed.

RESULTS

We identified 85 GCK gene mutations in 109 probands and 10 HNF1Α mutations in 12 probands. In GCK patients, the median neonatal weight and age at the first evaluation were lower than those found in patients with HNF1A mutations. Median fasting plasma glucose and impaired fasting glucose/impaired glucose tolerance frequency after oral glucose tolerance testing were higher in GCK patients, who also showed a lower frequency of diabetes than HNF1A patients.

CONCLUSIONS

GCK mutations are the prevailing cause of MODY (63.4%) when the index case is recruited in Italian children with incidental hyperglycemia.Between 1992–1999, the Italian Society of Pediatric Endocrinology and Diabetology (ISPED) Study Group on childhood pre-diabetes recruited 748 individuals with incidental hyperglycemia to be screened for markers of type 1 diabetes (1,2). Among autoantibody-negative subjects, a significant number (∼23%) met the criteria for clinical diagnosis of maturity-onset diabetes of the young (MODY), i.e., two or three consecutive generations with hyperglycemia diagnosed before age 25 years (3,4). Alterations in at least six different genes cause MODY (3), with mutations of the glucokinase (GCK) and hepatocyte nuclear factor 1α (HNF1Α) genes accounting for up to 85% of MODY in Europe. Defects of other MODY genes are quite rare (3). The aim of this study was to screen for GCK and HNF1Α genes in 172 Italian children with incidental hyperglycemia and clinical diagnosis of MODY.