Etiologic distribution and clinical characteristics of pediatric diabetes in 276 children and adolescents with diabetes at a single academic center

Abstract

Background The prevalence of monogenic diabetes is estimated to be 1.1–6.3% of patients with diabetes mellitus (DM) in Europe. The overlapping clinical features of various forms of diabetes make differential diagnosis challenging. Therefore, this study investigated the etiologic distribution and clinical characteristics of pediatric diabetes, including monogenic diabetes, who presented at a single tertiary center over the last 20 years. Methods This study included 276 consecutive patients with DM diagnosed before 18 years of age from January 2000 to December 2019 in Korea. Clinical features, biochemical findings, β-cell autoantibodies, and molecular characteristics were reviewed retrospectively. Results Of the 276 patients, 206 patients (74.6%), 49 patients (17.8%), and 21 patients (7.6%) were diagnosed with type 1 DM, type 2 DM, and clinically suspected monogenic diabetes, respectively. Among 21 patients suspected to have monogenic diabetes, 8 patients had clinical maturity-onset diabetes of the young (MODY), and the remaining 13 patients had other types of monogenic diabetes. Among them, genetic etiologies were identified in 14 patients (5.1%) from 13 families, which included MODY 5, transient neonatal DM, developmental delay, epilepsy, and neonatal diabetes (DEND) syndrome, Wolfram syndrome, Donohue syndrome, immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome, Fanconi-Bickel syndrome, Wolcott-Rallison syndrome, cystic fibrosis-related diabetes, and maternally inherited diabetes and deafness. Conclusions Genetically confirmed monogenic diabetes accounted for 5.1% of patients evaluated at a single tertiary center over 20-year period. Based on the findings for our sample, the frequency of mutations in the major genes of MODY appears to be low among pediatric patients in Korea. It is critical to identify the genetic cause of DM to provide appropriate therapeutic options and genetic counseling.

Applications of genomic research in pediatric endocrine diseases

“…21) Genetically confirmed monogenic diabetes accounted for 5.1% of patients in a singlecenter study in Korea. 65) In targeted gene panel sequencing of 109 Korean patients with suspected monogenic DM, 21% of the patients harbored patho genic or likely pathogenic variants. 66) The characteristics of patients with pathogenic or likely pathogenic variants include a lower BMI, higher MODY probability, and lower Cpeptide levels.…”

“…Monogenic diabetes is characterized by a Mendelian inheritance pattern with a large effect size of causal variants and minimal environmental contribution.21) Molecular diagnosis using NGS is also useful for monogenic diabetes as described previously [ 21 ]. Genetically confirmed monogenic diabetes accounted for 5.1% of patients in a single-center study in Korea [ 65 ]. In targeted gene panel sequencing of 109 Korean patients with suspected monogenic DM, 21% of the patients harbored pathogenic or likely pathogenic variants [ 66 ].…”

Further evidence supporting the role of DUT gene in diabetes with bone marrow failure syndrome

“…The combination of diabetes and extra pancreatic features raises the possibility of monogenic diabetes mellitus (MGD), which accounts for 1%–6.3% of diabetes caseload in children and young adults (Delvecchio et al, 2017; Kim et al, 2021). However, identifying this rare form of diabetes can guide the clinical management for the patients and their families (Hattersley et al, 2018).…”