Phenotypic heterogeneity in the diagnosis of MODY. An evidence-based approach to clinical diagnosis

Abstract

To date, 14 genes related to MODY (from the acronym in English maturity onset diabetes of the young) are recognized, however, the epidemiological variability with respect to maturity-onset diabetes of youth (MODY) is well known, refers to a heterogeneous group of monogenic forms of diabetes caused mainly by defects in insulin secretion. The individual MODY subtypes are distinct entities that are defined by their underlying mutations. MODY caused by mutations in glucokinase (GCK-MODY, MODY2) and hepatocyte nuclear factor 1-alpha (HNF1A-MODY, MODY3) are the most prevalent forms, involving around three quarters of all patients with MODY. The role of widespread genetic testing for MODY is controversial, given the associated cost, although that has fallen dramatically. Furthermore, the impact of a definitive MODY diagnosis can be significant, especially for young individuals misdiagnosed with type 1 diabetes; These patients can often stop insulin and transition to SU therapy, with improved glycemic control. In the midst of a social reality that imposes limitations to establish diagnoses of high technical complexity as is the case of MODY, it is imperative to propose basic clinical and paraclinical alternatives that allow establishing the highest degree of precision at the lowest cost, part of this premise is narrative review that will allow the clinician to refine the diagnosis in diabetes.