Identifying monogenic diabetes in a pediatric cohort with presumed type 1 diabetes

Pediatr Diabetes. 2015 May;16(3):227-33. doi: 10.1111/pedi.12150. Epub 2014 Aug 1.


Objective: Monogenic diabetes (MD) is rare and can often be confused with type 1 diabetes (T1D) in a pediatric cohort. We sought to determine clinical criteria that could optimally identify candidates for genetic testing of two common forms of MD that alter therapy: glucokinase (GCK) and hepatocyte nuclear factor 1 alpha (HNF1α).

Research design and methods: We performed a retrospective chart review of 939 patients with a presumed diagnosis of T1D, 6 months-20 yr of age, and identified four clinical criteria that were unusual for T1D and could warrant further evaluation for MD: (i) negative pancreatic autoantibodies, (ii) evidence of prolonged endogenous insulin production, or (iii) strong family history of diabetes in multiple generations. One hundred and twenty-one patients were identified as having one or more of these high-risk clinical criteria and were offered screening for mutations in GCK and HNF1α; 58 consented for genetic testing.

Results: Of 58 patients with presumed T1D who underwent genetic testing, four were found to have GCK and one had HNF1α. No patients with only one high-risk feature were found to have MD. Of 10 patients who had two or more high risk criteria, five had MD (50%).

Conclusion: A high frequency of MD from mutations in GCK/HNF1α may be identified among pediatric diabetic patients originally considered to have T1D by performing genetic testing on those patients with multiple clinical risk factors for MD.

Keywords: MODY; diabetes mellitus type 1; genetic testing; pediatrics.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Diabetes Mellitus / diagnosis
  • Diabetes Mellitus / genetics*
  • Diabetes Mellitus, Type 1 / diagnosis
  • Glucokinase / genetics*
  • Hepatocyte Nuclear Factor 1-alpha / genetics*
  • Humans
  • Infant
  • Retrospective Studies
  • Young Adult


  • HNF1A protein, human
  • Hepatocyte Nuclear Factor 1-alpha
  • Glucokinase