Maturity-onset diabetes of the young (
MODY) is a clinically heterogeneous group of monogenic disorders characterized by autosomal dominant inheritance of young-onset, non-
insulin-dependent diabetes. The genes involved are important in beta cell development, function and regulation and lead to disorders in
glucose sensing and insulin secretion. Heterozygous GCK mutations cause impaired
glucokinase activity resulting in stable, mild hyperglycaemia that rarely requires treatment. HNF1A mutations cause a progressive
insulin secretory defect that is sensitive to sulphonylureas, most often resulting in improved glycaemic control compared with other diabetes treatment.
MODY owing to mutations in the HNF4A gene results in a similar phenotype, including sensitivity to sulphonylurea treatment. HNF1B mutations most frequently cause developmental renal disease (particularly renal
cysts) but may also cause
MODY in isolation or may cause the
renal cysts and diabetes syndrome (RCAD syndrome). Mutations in NEUROD1, PDX1 (IPF1), CEL and INS are rare causes of
MODY.
MODY is often misdiagnosed as type 1 or
type 2 diabetes. However, a correct genetic diagnosis impacts treatment and identifies at-risk family members. Thus, it is important to consider a diagnosis of
MODY in appropriate individuals and to pursue genetic testing to establish a molecular diagnosis.