Monogenic diabetes mellitus in youth - The MODY syndromes

Early-onset diabetes inherited as an autosomal dominant (monogenic) trait constitutes maturity onset diabetes of the young (MODY). Classic MODY is observed predominantly in whites, develops before age 25, lacks ketosis, and generally is not insulin-treated. Fewer than one in 20 cases of diabetes in white children is caused by MODY. Atypical diabetes mellitus (ADM) is a MODY subtype that is oberved in at least 10% of African-American youth with diabetes. ADM presents as acute-onset diabetes, usually associated with weight loss, ketosis, and frequent diabetic ketoacidosis. Mutations in hepatocyte nuclear factor-4 alpha (HNF-4 alpha); MODY1), glucokinase (MODY2), hepatocyte nuclear factor-lot (HNF-1 alpha; MODY3), insulin promoter factor-1 (IPF-1; MODY4), and hepatocyte nuclear factor-1 beta (HNF-1 beta; MODY5) have been identified as causes of MODY. These monogenic syndromes have been studied to investigate the inheritance and pathophysiology of type 2 diabetes. Clinicians should be able to diagnose MODY because confusion with type 1 diabetes can lead to inappropriate patient management and inappropriate patient expectations.