Maturity-onset diabetes of the young: Molecular genetics, clinical manifestations, and therapy

Monogenic diabetes, accounting for 1-3% of diabetes cases, results from mutations that impair pancreatic β-cell function. Monogenic forms of diabetes are often misdiagnosed as either type 1 or type 2 diabetes. A molecular diagnosis based on an emerging genetic classification enables personalized treatment, better prediction of disease progression, as well as screening, early diagnosis, and genetic counseling of family members. Historically, monogenic forms of diabetes were termed maturity-onset diabetes of the young (MODY). The different MODY subtypes differ in age of onset, manifestation of hyperglycemia, patterns of glucose-stimulated insulin secretion, and response to treatments. Furthermore, several monogenic forms of childhood and adolescent diabetes are associated with extrapancreatic manifestations and can feature a range of genetic syndromes. In this chapter, monogenic β-cell diabetes subtypes will be described according to their molecular etiologies and categorized based on their clinical implications.