Mody

Abstract

Maturity-onset diabetes of the young (MODY) is a heterogeneous group of monogenic causes of beta-cell dysfunction and diabetes arising in children and young adults. Making an accurate diagnosis of MODY is important for establishing the correct management that differs from other common types of diabetes. Although many genes may be associated with monogenic diabetes, heterozygous mutations in 6 of them are responsible for the majority of cases of MODY. These are glucokinase gene, three hepatocyte nuclear factors (HNF) genes, and 2 genes, ABCC8 and KCNJ11, which encode the subunits of the ATP-dependent potassium channel in pancreatic beta cells. GCK-MODY and HNF1A-MODY are the most common subtypes. The clinical presentation of MODY subtypes has been reported to differ according to the gene involved. However, except in patients with GCK-MODY whose phenotype is very homogeneous, in most cases the penetrance and expressivity of a given gene mutation vary greatly among patients and, conversely, alterations in various genes may lead to similar phenotypes. Moreover, differential diagnosis among more common forms of diabetes may be difficult, particularly with type 2 diabetes. Thus, careful assessment of the personal and family histories of patients with diabetes is mandatory to select those in whom genetic screening is worthwhile.