Researchers find cause for neonatal diabetesBy John Easton
Medical Center Public Affairs
University geneticists and physicians have collaborated to identify the cause of a rare form of diabetes that affects newborn children.
In a report in the May 24 issue of The New England Journal of Medicine, an international team of researchers from Chicago, the University of Bergen, Norway, and the San Raffaele Scientific Institute, Italy, describes two cases of neonatal diabetes resulting from a complete deficiency of glucokinase, an enzyme that plays a crucial role in the regulation of blood-sugar levels.
Permanent neonatal diabetes mellitus is a rare disorder, occurring in about one in 400,000 live births. The two female children described in the journal paper, one Norwegian, the other Italian, required insulin treatment beginning soon after birth.
We believe this is the most common cause of permanent neonatal diabetes and urge physicians to look for glucokinase mutations in infants with diabetes, especially if the child has relatives with elevated blood sugar, said senior author Graeme Bell, the Louis Block Professor in Biochemistry & Molecular Biology, Medicine and Human Genetics.
In 1992, Bell led a team that discovered that glucokinase mutations were one cause of a sub-type of diabetes called maturity onset diabetes of the young, or MODY. That defect appears to be relatively common and underdiagnosed.
Finding glucokinase mutations that result in relatively mild disease as well as severe neonatal diabetes makes us suspect that there is a spectrum of glucose-regulation disorders that can be traced to different abnormalities of this gene, said Bell.
Both children described in the journal paper have mutations in both of their copies of the glucokinase gene. The mutations, however, are different in these two children. The Italian girl has two copies of a different mutation of the glucokinase gene than the Norwegian girl. But tests showed that both the Norwegian and Italian mutations rendered the enzyme inactive. Neither child with neonatal diabetes secretes any insulin.
The genetics of diabetes have proved to be very complex. Bells team has isolated four different genes that cause MODY, and last year pinpointed the first of several genes that increase susceptibility to the most common form of diabetes.
This new role for glucokinase is another piece of the puzzle, Bell said. Not only are there many genes involved, but also different mutations and combinations may cause differing forms of the disease.
Researchers from the University of Pennsylvania; the National Hospital, Oslo, Norway; and Vanderbilt University, Nashville, Tenn., contributed to this study.