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Journal of pediatric endocrinology & metabolism : JPEM, vol.35, no.12, pp.1528-1536, 2022 (SCI-Expanded)
Objectives The aim of this study is to determine the clinical and molecular characteristics enabling differential diagnosis in a group of Turkish children clinically diagnosed with MODY and identify the cut-off value of HbA(1c), which can distinguish patients with GCK variants from young-onset type 1 and type 2 diabetes. Methods The study included 49 patients from 48 unrelated families who were admitted between 2018 and 2020 with a clinical diagnosis of MODY. Clinical and laboratory characteristics of the patients at the time of the diagnosis were obtained from hospital records. Variant analysis of ten MODY genes was performed using targeted next-generation sequencing (NGS) panel and the variants were classified according to American Collage of Medical Genetics and Genomics (ACMG) Standards and Guidelines recommendations. Results A total of 14 (28%) pathogenic/likely pathogenic variants were detected among 49 patients. 11 variants in GCK and 3 variants in HNF1A genes were found. We identified four novel variants in GCK gene. Using ROC analysis, we found that best cut-off value of HbA(1c) at the time of diagnosis for predicting the subjects with a GCK variant among patients suspected to have MODY was 6.95% (sensitivity 90%, specificity 86%, AUC 0.89 [95% CI: 0.783-1]). Most of the cases without GCK variant (33/38 [86%]) had an HbA(1c) value above this cutoff value. We found that among participants suspected of having MODY, family history, HbA(1c) at the time of diagnosis, and not using insulin therapy were the most differentiating variables of patients with GCK variants. Conclusions Family history, HbA(1c) at the time of diagnosis, and not receiving insulin therapy were found to be the most distinguishing variables of patients with GCK variants among subjects suspected to have MODY.