An underdiagnosed type of diabetes: the MODY syndromes. Pathophysiology, clinical presentation and renal disease progression.

Maturity onset diabetes of the young (MODY syndrome) is characterized by a non-ketotic type II diabetes mellitus (DM) that is inherited by an autosomal dominant mode and appears in young people, <25 yrs old, with a prominent family history of DM in successive generations from one side of the parents. Usually, it presents as asymptomatic mild hyperglycemia, which can be undetected for prolonged periods. Therefore, diagnosis can be made rather late in adulthood and diabetic complications could be present at diagnosis. It is estimated that it could account for 1-5% of cases in the US and other industrialized countries and can result from mutations on any of six different genes that are expressed in the beta-cells of the pancreas. These genes encode the glycolytic enzyme glucokinase (MODY 2) and the other five encode the transcription factors hepatocyte nuclear factor (HNF) 4alpha (MODY 1), HNF-1alpha (MODY 3), HNF-1beta (MODY 5), insulin promoter factor 1 (IPF-1) (MODY 4) and neurogenic differentiation factor-1 (NeuroD1) (MODY 6).