Childhood obesity complicating the differential diagnosis of maturity-onset diabetes of the young and type 2 diabetes.

Objective: To describe a proband with features of type 2 diabetes who was found to have concomitant maturity-onset diabetes of the young (MODY) and the consequent multigeneration genetic analysis.

Design: Familial genetic analysis.

Setting: Tertiary university medical center.

Participants: The proband was a 13.5-yr-old boy with marked non-ketotic hyperglycemia, obesity, systolic hypertension, and insulin resistance. His mother, maternal aunt, grandmother, and great grandmother had diabetes; his father was obese and had early ischemic heart disease.

Interventions: Clinical examination, laboratory work-up, and DNA study.

Outcome Measures: Mutation in hepatocyte nuclear factor-1alpha gene, the most common cause of MODY.

Results: The proband showed elevated C-peptide level and was negative for beta-cell antibodies. On genetic analysis for MODY, the 291fsinsC mutation was identified in all affected family members. A younger sister who was obese but had no signs of impaired glucose tolerance was also tested on the basis of these findings and was found to have the same mutation.

Conclusions: The patient, who presented with apparent type 2 diabetes, had concomitant MODY 3, inherited from his mother's side, and some features of type 2 diabetes secondary to marked obesity. This combination probably caused an earlier and more severe presentation of the disease and had significant implications for medical management. A search for MODY mutations should be considered in patients with a history of diabetes in three generations of one side of the family, even those in whom the clinical picture resembles type 2 diabetes.