CUKRZYCA MODY – PODŁOŻE MOLEKULARNE, CECHY KLINICZNE I POSTĘPOWANIE DIAGNOSTYCZNE

Abstract

Maturity-onset diabetes of the young (MODY) is a monogenic disorder with autosomal dominant inheritance. MODY is a rarely diagnosed form of diabetes, its incidence, depending on the population, is estimated at 1-5% of children with diabetes. MODY diabetes currently includes 14 forms of diabetes with different etiology. Each of the MODY subtypes is conditioned by a mutation in one of the 14 identified genes: HNF4A, GCK, HNF1A, PDX1, HNF1B, NEUROD1, KLF11, CEL, PAX4, INS, BLK, ABCC8, KCNJ11, APPL1. The most frequently recognized subtypes of MODY are conditioned by mutations of the HNF1A (30-65%), GCK (30-60%), HNF4A (5-10%) and HNF1B (5%) genes. MODY is characterized by the following features: 1) mild fasting hyperglycemia, 2) onset of symptoms before the age of 25, 3) lack of autoantibodies against pancreatic beta-cell antigens and features typical of type 2 diabetes (insulin resistance, obesity). Individual subtypes of MODY diabetes are characterized by a different spectrum of clinical symptoms and different age of onset. GCK gene mutations cause mild, asymptomatic fasting hyperglycemia, usually not requiring appropriate treatment. HNF1A and HNF4A gene mutations are associated with progressive pancreatic β-cell dysfunction and hyperglycemia, which may lead to microvascular complications, in the HNF1B- MODY subtype there are concomitant developmental abnormalities. In the treatment of MODY, depending on the subtype, diet, sulfonylureas or other oral hyperglycemic agents are applied and insulin therapy may be required later in life and during pregnancy. Next-generation sequencing (NGS) technique using a commercial gene panel is used in the molecular diagnosis of MODY diabetes. The knowledge of the genetic etiology of diabetes and the determination of the MODY subtype is of significant practical importance in the prognosis of the course of the disease, it allows the selection of the optimal t reatment method, it is also the basis for screening of asymptomatic family members of the patient and genetic consueling.