Maturity-onset diabetes of the young (MODY) is a heritable form of diabetes mellitus that results from a primary defect in insulin secretion. MODY is diagnosed clinically in patients with early-onset hyperglycemia or non-insulin-dependent diabetes who have a family history of impaired glucose metabolism in at least 2 consecutive generations, with at least 1 family member diagnosed before age 25. To date, 9 different subtypes of MODY have been described. MODY2 and MODY3 account for the majority of genetically diagnosed MODY cases. MODY2 is caused by variants in the glucokinase (GCK) gene and is characterized by mild hyperglycemia that is persistent but stable. It is often treated successfully with dietary and lifestyle changes alone. MODY3 is caused by variants in the hepatocyte nuclear factor 1 alpha (HNF1A) gene, and is characterized by progressive pancreatic beta-cell dysfunction. As a result, MODY3 patients develop diabetes in adolescence or early adulthood, and are at risk of significant complications if blood glucose levels are not well
controlled. Patients with MODY3 are often treated successfully with sulphonylurea medications. The remaining 7 types of MODY are due to alterations in the following genes: hepatocyte nuclear factor 4 alpha (HNF4A) (MODY1); insulin promoter factor 1 (IPF1) (MODY4); HNF1 homeobox B (HNF1B) (MODY5); neurogenic differentiation 1 (NEUROD1) (MODY6); Kruppel-like factor 11 (KLF11) (MODY7); carboxyl ester lipase (CEL) (MODY8); and paired box gene 4 (PAX4) (MODY9). The majority of patients with these MODY subtypes exhibit features similar to those seen in MODY3, although patients with MODY5 typically have kidney abnormalities, and patients with MODY8 may have exocrine pancreatic dysfunction. All MODY subtypes are inherited in an autosomal dominant manner.