Persistent mild hyperglycaemia in several family members: discovery of a novel mutation Glu268Stop in the glucokinase gene (MODY 2)
Abstract
Glycaemia 6.9 mmol/L was randomly found in a 4-year-old boy. Within the subsequent 7 years, his fasting blood glucose varied between 5.7 and 8.8 mmol/L.
OGTT did not meet criteria for diabetes mellitus and first phase insulin release was not significantly decreased. HbA1c fluctuated at the upper normal range (5.4 - 6.7 %; normal values 4.0 - 6.4 %).
The boy is not being treated and has no diet restrictions. In the boy's father, glycaemia 7.7 mmol/L was randomly estimated at age 34 years, and in the boy's grandfather (father's father), 6.2 mmol/L at 33 years.
Both were recommended to comply with diabetic diet. The grandfather's status remained unchanged within the subsequent 29 years.
In the younger patient's brother, blood glucose 8.0 mmol/L was measured between two breast-feedings at age 4 months. His fasting glycaemia was 5.8 mmol/L and the HbA1c level 6.0 %.
We found a novel nonsense mutation of the glucokinase gene Glu268Stop in the patient, in his brother and in their father. This mutation leads to a dramatic truncation of the enzyme molecule.
Thus, autosomal dominant transmission of MODY 2, a benign subtype of MODY diabetes, occurs within the family. According to recent views, this disorder is usually not progressive and does not cause clinical symptoms throughout the lifespan.
No therapy is probably required.