Diagnosis and treatment of neonatal diabetes: a United States experience.

DRTC - Vanderbilt University

Authors

Støy J, Greeley SA, Paz VP, Ye H, Pastore AN, Skowron KB, Lipton RB, Cogen FR, Bell GI, Philipson LH, United States Neonatal Diabetes Working Group,

Journal

Pediatric diabetes,2008

Abstract

BACKGROUND/OBJECTIVE: Mutations in KCNJ11, ABCC8, or INS are the cause of permanent neonatal diabetes mellitus in about 50% of patients diagnosed with diabetes before 6 months of age and in a small fraction of those diagnosed between 6 and 12 months. The aim of this study was to identify the genetic cause of diabetes in 77 consecutive patients referred to the University of Chicago with diabetes diagnosed before 1 yr of age. METHODS: We used Oragene DNA Self-Collection kit to obtain a saliva sample for DNA. We sequenced the protein-coding regions of KCNJ11, ABCC8, and INS using standard methods. RESULTS: We enrolled 32 patients diagnosed with diabetes before 6 months of age and 45 patients diagnosed between 6 and 12 months. We identified a mutation in KCNJ11 in 14 patients from 12 families and in INS in 7 patients from 4 families. Three of the patients with an INS mutation were diagnosed with diabetes between 6 and 12 months of age. Finally, we found that two patients had an abnormality of chromosome 6q24 associated with transient neonatal diabetes mellitus. CONCLUSIONS: We were able to establish a genetic cause of diabetes in 63% of patients diagnosed with diabetes before 6 months of age and in 7% of patients diagnosed between 6 and 12 months. Genetic testing, which is critical for guiding appropriate management, should be considered in patients diagnosed with diabetes before 1 yr of age, especially if they are autoantibody negative, although the presence of autoantibodies does not rule out a monogenic cause.