Monogenic diabetes MODY in childhood: a retrospective study of patients diagnosed at the Department of Pediatrics, University Hospital in Pilsen in 2000–2017

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Authors: J. Zamboryová ¹; R. Pomahačová ¹; K. Fiklík ¹; L. Elblová ²; J. Sýkora ¹
Authors place of work: Dětská klinika Lékařské fakulty v Plzni, Univerzity Karlovy v Praze a Fakultní nemocnice, Plzeň ¹; Pediatrická klinika 2. lékařské fakulty Univerzity Karlovy a Fakultní nemocnice Motol, Praha ²
Published in the journal: Čes-slov Pediat 2019; 74 (1): 16-21.
Category:

Summary

Objective:

The aim of the retrospective study was to investigate the incidence of monogenic diabetes MODY (Maturity Onset Diabetes of the Young) in patients examined at the Department of Pediatrics, University Hospital in Pilsen in 2000–2017. 16 patients with monogenic diabetes were included in the study: 9 girls and 7 boys with an average age of 10.2 years (ranging from 3 to 17 years).

Methods:

The following parameters were retrospectively analysed in all patients: sex, age at the time of diagnosis, familial incidence of the disease, baseline parameters of carbohydrate metabolism (fasting blood glucose, glycated hemoglobin HbA1c), oral glucose tolerance test (oGTT), intravenous glucose tolerance test (ivGTT), and islet cell autoantibodies. The diagnosis of MODY diabetes was confirmed by molecular genetic testing of GCK, HNF1A, HNF4A a HNF1B genes.

Results:

In the analysed group, 13 cases of GCK-MODY and 3 cases of HNF-diabetes (HNF4A-MODY, HNF1A-MODY, HNF1B-MODY) were confirmed. Patients with GCK-MODY had a slightly elevated fasting blood glucose (6.3–7.3 mmol/l) and HbA1c (median of 46 mmol/mol), impaired glucose tolerance on the oGTT in 94%, physiological first-phase insulin response (FPIR) during ivGTT, and negative islet cell autoantibodies. In one family, the most frequently described mutation in the glucokinase gene p.Glu40Lys in the Czech Republic was confirmed. Patients with HNF-diabetes had a diabetic curve on the oGTT, decreased FPIR during ivGTT, median HbA1c of 64 mmol/mol, and negative islet cell autoantibodies. The diagnosis of GCK-MODY in the families allowed discontinuation of treatment with insulin and oral antidiabetic drugs (OADs) and, in the case of HNF-diabetes, switching from insulin to OADs.

Conclusion:

The differential diagnosis in patients with impaired glucose tolerance or diabetes mellitus should include MODY diabetes. Confirmation or ruling out of the gene mutation predicts disease progression and proper choice of therapy. Knowledge of the gene mutation enables disease detection in the presymptomatic phase in the affected families.

Keywords:

molecular genetic testing – monogenic diabetes – MODY diabetes – oral glucose tolerance test

Zdroje

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