<abstract xmlns="http://www.w3.org/1999/xhtml"><bold>Objective.</bold> Mutations of the <italic>KCNJ11</italic> gene are the most common cause of the permanent neonatal diabetes mellitus (PNDM). Majority of people with KNCJ11-PNDM have a de-novo mutation. We aimed to compare diabetes phenotype in two children and their mothers with PNDM carrying the same sulfonylurea-sensitive <italic>KCNJ11</italic> variants.<bold>Methods.</bold> We have compared glibenclamide (sulfonylurea) dose, C-peptide, and HbA1c serum levels in two children and their mothers with PNDM up to 5.5-year follow-up. All of them were carrying a heterozygous activating <italic>KCNJ11</italic> pathogenic variant (p.R201H in Family 1 or p.H46Y in Family 2). The mothers were initially treated with insulin and successfully switched to sulfonylurea at the age of 24 and 11 years, respectively. Both children were treated with sulfonylurea since the diagnosis of PNDM.<bold>Results.</bold> Glibenclamide dose was similar in both children (0.02–0.03 mg/kg/day), but lower compared to their mothers (0.1–0.4 mg/kg/day) (p&lt;0.002). Fasting serum C-peptide levels were also lower in children (70–210 pmol/l) than in their mothers (263–720 pmol/l) (p&lt;0.002), but no significant differences were observed in postprandial C-peptide levels. HbA1c was lower only in the son of SVK4 (Family 2) compared to his mother, as she had poor adherence to the sulfonylurea therapy during the first years after the sulfonylurea switch.<bold>Conclusions.</bold> Evaluation of the treatment in people with sulfonylurea-sensitive KNCJ11-PNDM should respect the age of patients together with the type of mutation and duration of diabetes at therapy start and may differ within one family.</abstract>

Objective. Mutations of the KCNJ11 gene are the most common cause of the permanent neonatal diabetes mellitus (PNDM). Majority of people with KNCJ11-PNDM have a de-novo mutation. We aimed to compare diabetes phenotype in two children and their mothers with PNDM carrying the same sulfonylurea-sensitive KCNJ11 variants.Methods. We have compared glibenclamide (sulfonylurea) dose, C-peptide, and HbA1c serum levels in two children and their mothers with PNDM up to 5.5-year follow-up. All of them were carrying a heterozygous activating KCNJ11 pathogenic variant (p.R201H in Family 1 or p.H46Y in Family 2). The mothers were initially treated with insulin and successfully switched to sulfonylurea at the age of 24 and 11 years, respectively. Both children were treated with sulfonylurea since the diagnosis of PNDM.Results. Glibenclamide dose was similar in both children (0.02–0.03 mg/kg/day), but lower compared to their mothers (0.1–0.4 mg/kg/day) (p<0.002). Fasting serum C-peptide levels were also lower in children (70–210 pmol/l) than in their mothers (263–720 pmol/l) (p<0.002), but no significant differences were observed in postprandial C-peptide levels. HbA1c was lower only in the son of SVK4 (Family 2) compared to his mother, as she had poor adherence to the sulfonylurea therapy during the first years after the sulfonylurea switch.Conclusions. Evaluation of the treatment in people with sulfonylurea-sensitive KNCJ11-PNDM should respect the age of patients together with the type of mutation and duration of diabetes at therapy start and may differ within one family.

Comparison of diabetes phenotype in children and their mothers with permanent neonatal diabetes mellitus carrying the same <italic>KCNJ11</italic> variants

Children Diabetes Centre of the Slovak Republic at the Department of Paediatrics

Medical Faculty of Comenius University and National Institute for Children′s Diseases

Endocrine Regulations

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Comparison of diabetes phenotype in children and their mothers with permanent neonatal diabetes mellitus carrying the same  variants

Objective. Mutations of the KCNJ11 gene are the most common cause of the permanent neonatal diabetes mellitus (PNDM). Majority of people with KNCJ11-PNDM have...

Comparison of diabetes phenotype in children and their mothers with permanent neonatal diabetes mellitus carrying the same KCNJ11 variants

Published Online: Nov 24, 2020

Page range: 260 - 265

DOI: https://doi.org/10.2478/enr-2020-0029

Keywords
permanent neonatal diabetes mellitus, KCNJ11, children, mothers, diabetes control, sulfonylurea, C-peptide

© 2020 Juraj Stanik et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Comparison of diabetes phenotype in children and their mothers with permanent neonatal diabetes mellitus carrying the same KCNJ11 variants

Published Online: Nov 24, 2020

Page range: 260 - 265

DOI: https://doi.org/10.2478/enr-2020-0029

Keywordspermanent neonatal diabetes mellitus, KCNJ11, children, mothers, diabetes control, sulfonylurea, C-peptide

© 2020 Juraj Stanik et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Keywords
permanent neonatal diabetes mellitus, KCNJ11, children, mothers, diabetes control, sulfonylurea, C-peptide