Maturity-onset diabetes of the young (MODY) is a group of hereditary diseases with a mainly dominant inheritance pattern. It is responsible for approximately 1-2% of all cases of diabetes, but it is an underdiagnosed disease. Patients with MODY diabetes are often incorrectly diagnosed with type 1 diabetes (~10% of cases) or with type 2 diabetes (2–5% of cases).
It is characterized by an early onset of hyperglycemia, typically before age 25 (although diagnosis can be reached at a later age). Unlike type 1 diabetes, MODY patients do not usually require insulin treatment and do not show pancreatic islet-cell antibodies (although some cases of type 1 diabetes coexisting with MODY have been reported) or ketoacidosis, while it is common to find evidence of endogenous insulin production after the honeymoon period (3-5 years after the diabetes starts). Unlike type 2 diabetes, MODY is not usually associated with obesity or acanthosis nigricans, and its progression is usually slow and gradual. In addition to diabetes, patients may present with other clinical manifestations of varying types and degrees of severity depending on the type of causal mutation. Risk of early atherosclerosis is increased in patients with MODY diabetes who are not receiving appropriate treatment.
Another type of monogenic diabetes is neonatal diabetes mellitus, which can be expressed following either a dominant or a recessive inheritance pattern. It is defined as the occurrence of hyperglycemia during the first six months of life. The most common clinical presentation is a marked hyperglycemia and a low weight at birth due to the decrease or absence of intrauterine insulin secretion, and ketoacidosis is uncommon. Pancreatic autoantibodies are negative, and concentrations of C-peptide are reduced. Diagnosis is made in children younger than 12 months with persistent hyperglycemia (plasma glucose concentrations >150-200 mg/dl).
The latest recommendations from international organizations and guidelines by expert working groups recommend genetic testing in patients with suspicion of monogenic diabetes. The American Diabetes Association recommends that all children diagnosed with diabetes during their first 6 months of life be immediately subjected to genetic testing to detect neonatal diabetes and that those children and patients diagnosed in adulthood who meet the criteria for suspicion of MODY diabetes be genetically tested. Mutations responsible for the disease are identified in more than 90% of cases with a clear suspicion of MODY diabetes.
