title: Identifying monogenic diabetes in a pediatric cohort with presumed type 1 diabetes.
abstract: 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).
  
  
  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%).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Pediatric Endocrinology, Diabetes, and Metabolism, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Rachelle G
authors.initials: RG
authors.lastname: Gandica
authors.forename: Wendy K
authors.initials: WK
authors.lastname: Chung
authors.forename: Liyong
authors.initials: L
authors.lastname: Deng
authors.forename: Robin
authors.initials: R
authors.lastname: Goland
authors.forename: Mary Pat
authors.initials: MP
authors.lastname: Gallagher
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003920:Diabetes Mellitus / Q000175:diagnosis / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis; D005941:Glucokinase / Q000235:genetics*; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics*; D006801:Humans; D007223:Infant; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: C496487:HNF1A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D005941:Glucokinase
keywords: MODY; diabetes mellitus type 1; genetic testing; pediatrics
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