Introduction-Aim: MODY;It is an autosomal dominant, rare type of diabetes that occurs in young people as a result of mutations of beta cell function and genes involved in insulin secretion. The cases may be misdiagnosed as Type1 and Type2 diabetes. Considering that MODY is clinically and genetically heterogeneous, the findings should be evaluated correctly. It is important to define the clinical-laboratory characteristics of diagnosis and follow-up of patients diagnosed genetically as MODY. The aim of this study was to investigate the clinical and laboratory features of patients with MODY and to investigate the relationship between genotype and phenotype.
Methods: A total of 44MODY cases were included in the study. Mutations inHNF4A,GCK,HNF1A,PDX1,HNF1B,NEUROD1,KLF11,CEL,PAX4,INSandBLK genes were studied by Sanger sequence and targeted next-generation sequencing analysis method. The cases who were treated according to the MODY type and the follow-up data and were followed up for at least 3 years were included. Anthropometry, examination, blood glucose andHbA1C levels were evaluated at3-month intervals.
Results: The age of diagnosis of44patients withMODY(24 male) was9.4±4.7(1-17)years. Except for three cases, the height and weight were normal. 55% of the patients were diagnosed as random hyperglycemia, 36% with symptomatic hyperglycemia and 9% with ketosis. All cases had a family history of diabetes. Blood glukoz levels(97-664mg/dl), HbA1C(5.2-15.6%)and C-peptide levels(0.2-5.9ng/ml) were quite wide in the diagnosis. Only 2of44 cases had anti-GAD positivity and anti-insulin and işlet-cell-antibodies were negative in all cases. The most common mutation was found in 55%GCK gene (5 new mutations) while the other distribution was; KLF11-MODY(n=7;16%),HNF1A-MODY(n=6;13%),NEUROD1-MODY(n=2),HNF4A-MODY(n=2),PDX1-MODY,CEL-MODY(new mutation)and HNF1B-MODY mutation were detected in one case. All cases of GCK,NEUROD1,PDX1andCEL-MODYwere treated only with diet,HNF1A-MODY sulfanylurea treatment, 1 of metformin in KLF11-MODY, 5cases with intensive insulin,HNF4A and HNF1B-MODY.
Conclusion: In this study, it was found that the association with the presence of hyperglycemia, the presence of2-3 generations of diabetes in the family, anti-insulin and islet cell antibody negativity findings were strongly differentiated for MODY. Blood glucose levels, HbA1C and C-peptide levels were found to be in a wide spectrum according to genetic heterogeneity. The most common GCK mutation was 55% of all cases. The cases withGCK,NEUROD1,PDX1andCEL-MODY only with dietary treatment and HNF1A-MODY cases with sulfanilurea treatment, were found to be in good metabolic control during long-term follow-up.In other MODYtypes, it was observed that they needed intense insulin according to beta cell reserve.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology