title: Characteristics of maturity onset diabetes of the young in a large diabetes center.
abstract: Maturity onset diabetes of the young (MODY) is a monogenic form of diabetes caused by a mutation in a single gene, often not requiring insulin. The aim of this study was to estimate the frequency and clinical characteristics of MODY at the Barbara Davis Center. A total of 97 subjects with diabetes onset before age 25, a random C-peptide ≥0.1 ng/mL, and negative for all diabetes autoantibodies (GADA, IA-2, ZnT8, and IAA) were enrolled, after excluding 21 subjects with secondary diabetes or refusal to participate. Genetic testing for MODY 1-5 was performed through Athena Diagnostics, and all variants of unknown significance were further analyzed at Exeter, UK. A total of 22 subjects [20 (21%) when excluding two siblings] were found to have a mutation in hepatocyte nuclear factor 4A (n = 4), glucokinase (n = 8), or hepatocyte nuclear factor 1A (n = 10). Of these 22 subjects, 13 had mutations known to be pathogenic and 9 (41%) had novel mutations, predicted to be pathogenic. Only 1 of the 22 subjects had been given the appropriate MODY diagnosis prior to testing. Compared with MODY-negative subjects, the MODY-positive subjects had lower hemoglobin A1c level and no diabetic ketoacidosis at onset; however, these characteristics are not specific for MODY. In summary, this study found a high frequency of MODY mutations with the majority of subjects clinically misdiagnosed. Clinicians should have a high index of suspicion for MODY in youth with antibody-negative diabetes.
authors.affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Chambers
authors.affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Fouts
authors.affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO, USA.
authors.forename: Fran
authors.initials: F
authors.lastname: Dong
authors.affiliation: Department of Genetics, Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK.
authors.forename: Kevin
authors.initials: K
authors.lastname: Colclough
authors.affiliation: Athena Diagnostics, Worcester, MA, USA.
authors.forename: Zhenyuan
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Athena Diagnostics, Worcester, MA, USA.
authors.forename: Sat Dev
authors.initials: SD
authors.lastname: Batish
authors.affiliation: Athena Diagnostics, Worcester, MA, USA.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Jaremko
authors.affiliation: Department of Genetics, Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK.
authors.forename: Sian
authors.initials: S
authors.lastname: Ellard
authors.affiliation: Department of Genetics, Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Hattersley
authors.affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO, USA.
authors.forename: Georgeanna
authors.initials: G
authors.lastname: Klingensmith
authors.affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO, USA.
authors.forename: Andrea K
authors.initials: AK
authors.lastname: Steck
mesh_terms: D000293:Adolescent; D002096:C-Peptide / Q000097:blood; D002648:Child; D003120:Colorado / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology* / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation
chemical_list: D002096:C-Peptide
keywords: GCK; HNF1A; HNF4A; MODY