Next generation sequencing in the differential diagnosis of diabetes mellitus in children
Authors:   Saint-Petersburg State Pediatric Medical University, Saint Petersburg, Russian Federation, Ivanov D.O. , Turkunova M.E. ,   Saint-Petersburg State Pediatric Medical University, Saint Petersburg, Russian Federation, Ditkovskaya L.V. ,   Saint-Petersburg State Pediatric Medical University, Saint Petersburg, Russian Federation, Barbitoff Yu.A. ,   D.O.Ott Research Institute of Obstetrics, Gynecology and Reproductology, Saint Petersburg, Russian Federation, Serebryakova E.A. ,   D.O.Ott Research Institute of Obstetrics, Gynecology and Reproductology, Saint Petersburg, Russian Federation, Glotov O.S. ,   D.O.Ott Research Institute of Obstetrics, Gynecology and Reproductology, Saint Petersburg, Russian Federation, Glotov A.S. ,   D.O.Ott Research Institute of Obstetrics, Gynecology and Reproductology, Saint Petersburg, Russian Federation, Berseneva О.S. ,   I.I.Mechnikov North-Western State Medical University, Saint Petersburg, Russian Federation, Scorodok J.L. ,   Saint-Petersburg State Pediatric Medical University, Saint Petersburg, Russian Federation, Efimova O.A. ,   D.O.Ott Research Institute of Obstetrics, Gynecology and Reproductology, Saint Petersburg, Russian Federation, Zhelenina L.A. ,   Saint-Petersburg State Pediatric Medical University, Saint Petersburg, Russian Federation, Ivashchenko T.E. ,   D.O.Ott Research Institute of Obstetrics, Gynecology and Reproductology, Saint Petersburg, Russian Federation, Suspitsyn E.N. ,   D.O.Ott Research Institute of Obstetrics, Gynecology and Reproductology, Saint Petersburg, Russian Federation, Bashnina E.B. ,   I.I.Mechnikov North-Western State Medical University, Saint Petersburg, Russian Federation
Published: April 2022

In addition to type 1 and 2 diabetes mellitus (DM), endocrine disorders in children include hereditary forms of diabetes, such as maturity onset diabetes of the young (MODY). Since pathogenic mechanisms of chronic hyperglycemia in MODY are different from those in DM1 and DM2, it requires other therapeutic approaches. The diagnosis of MODY is confirmed by expensive molecular testing, such as next generation sequencing (NGS). Therefore, the strategy of choosing candidates for NGS is very important. Objective. To optimize the algorithm of choosing patients for NGS testing for DM type verification. Patients and methods. This study included 97 patients aged 1–18 years suspected of having MODY. We used NGS to confirm the diagnosis and identify polymorphisms in MODY-associated genes. Results. Fifty-three patients were found to have polymorphisms in MODY-associated genes, including GCK gene (MODY2) (n = 44), NHF1A gene (MODY3) (n = 8), and PAX4 gene (MODY9) (n = 1). Comparison of family histories of patients with MODY-associated polymorphisms and those in whom clinical diagnosis of MODY was not confirmed by NGS demonstrated significant differences: children with verified MODY were more likely to have first-degree relatives with some carbohydrate metabolism disorder (CMDs). Clinical, laboratory, and anthropometric parameters, as well as levels of insulin secretion and carbohydrate metabolism were similar in both groups. However, patients with non-confirmed MODY received insulin therapy more frequently than those with verified MODY as the majority of them were on a diet. Conclusion. NGS confirms the diagnosis of MODY in patients with different CMDs. A tailored approach should be used to choose patients for NGS to confirm MODY. Key words: monogenic diabetes mellitus in children, diabetes mellitus, next generation sequencing, GCK, HNF1A, MODY