Severe Developmental Delay, Epilepsy and Neonatal Diabetes (DEND) Syndrome: A Case Report

Muhd Alwi Muhd Helmi; Suhaimi Hussain

doi:10.15605/jafes.035.01.22

Authors

Muhd Alwi Muhd Helmi Kulliyya of Medicine, International Islamic University of Malaysia http://orcid.org/0000-0001-5259-6289
Suhaimi Hussain University Sains Malaysia http://orcid.org/0000-0002-7164-3076

DOI:

https://doi.org/10.15605/jafes.035.01.22

Keywords:

DEND syndrome, glibenclamide, congenital diabetes

Abstract

Developmental delay, Epilepsy and Neonatal Diabetes (DEND) syndrome is the most severe form of Permanent Neonatal Diabetes with KCNJ11 gene mutation which accounts for most of the cases. We report the first DEND syndrome in Malaysia with heterozygous missense mutation Q52R at KCNJ11 (Kir6.2) gene with delayed presentation beyond 6 months of age and failure to transition to glibenclamide. This report signifies the phenotypical variability among patients with the same genetic mutation and the different response to treatment.

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Author Biographies

Muhd Alwi Muhd Helmi, Kulliyya of Medicine, International Islamic University of Malaysia

Pediatric Department

Suhaimi Hussain, University Sains Malaysia

Paediatric Department, School of Medical Sciences

References

Koster JC, Kurata HT, Enkvetchakul D, Nichols CG. DEND mutation in Kir6. 2 (KCNJ11) reveals a flexible N-terminal region critical for ATP-sensing of the KATP channel. Biophys J. 2008;95(10):4689-97. https://www.ncbi.nlm.nih.gov/pubmed/18708460. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2576385. https://doi.org/10.1529/biophysj.108.138685.

Stanik J, Gasperikova D, Paskova M, et al. Prevalence of permanent neonatal diabetes in Slovakia and successful replacement of insulin with sulfonylurea therapy in KCNJ11 and ABCC8 mutation carriers. J Clin Endocrinol Metab. 2007;92(4):1276-82. https://www.ncbi.nlm.nih.gov/pubmed/17213273. https://doi.org/10.1210/jc.2006-2490.

Ashcroft FM, Puljung MC, Vedovato N. Neonatal diabetes and the KATP channel: From mutation to therapy. Trends Endocrinol Metab. 2017;28(5):377-87. https://www.ncbi.nlm.nih.gov/pubmed/28262438. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5582192. https://doi.org/10.1016/j.tem.2017.02.003.

Souza SW, Alcazar LP, Arakaki P, et al. Polymorphism E23K (rs5219) in the KCNJ11 gene in Euro-Brazilian subjects with type 1 and 2 diabetes. Genet Mol Res. 2017;16. https://www.ncbi.nlm.nih.gov/pubmed/28387875. https://doi.org/10.4238/gmr16029543.

Stenson PD, Mort M, Ball EV, Shaw K, Phillips AD, Cooper DN. The human gene mutation database: Building a comprehensive mutation repository for clinical and molecular genetics, diagnostic testing and personalized genomic medicine. Hum Gen. 2014;133(1):1-9. https://www.ncbi.nlm.nih.gov/pubmed/24077912. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3898141. https://doi.org/10.1007/s00439-013-1358-4.

Flanagan SE, Clauin S, Bellanné-Chantelot C, et al. Update of mutations in the genes encoding the pancreatic beta-cell K(ATP) channel subunits Kir6.2 (KCNJ11) and sulfonylurea receptor 1 (ABCC8) in diabetes mellitus and hyperinsulinism. Hum Mutat. 2009;30(2): 170-80. https://www.ncbi.nlm.nih.gov/pubmed/18767144. https://doi.org/10.1002/humu.20838.

Shimomura K, Maejima Y. KATP channel mutations and neonatal diabetes. Intern Med. 2017;56(18):2387-93. https://www.ncbi.nlm.nih.gov/pubmed/28824061. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5643163. https://doi.org/10.2169/internalmedicine.8454-16.

Ioacara S, Flanagan S, Fröhlich‐Reiterer E, Goland R, Fica S. First case of neonatal diabetes with KCNJ11 Q52R mutation successfully switched from insulin to sulphonylurea treatment. J Diab Investig. 2017;8(5):716-9. https://www.ncbi.nlm.nih.gov/pubmed/28083968. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5583959.

https://doi.org/10.1111/jdi.12620.

Singh P, Rao SC, Parikh R. Neonatal diabetes with intractable epilepsy: DEND syndrome. Indian J Pediatr. 2014;81(12):1387-8. https://www.ncbi.nlm.nih.gov/pubmed/24912436. https://doi.org/10.1007/s12098-014-1486-4.

Hattersley A. Inpatient protocol for the transfer of patients with Kir6.2 and SUR1 mutations from insulin to sulphonylureas in patients with PNDM [Treatment protocol ]. Unpublished.

Rubio-Cabezas O, Flanagan SE, Damhuis A, Hattersley AT, Ellard S. KATP channel mutations in infants with permanent diabetes diagnosed after 6 months of life. Pediatr Diabetes. 2012;13(4):322-5.

https://www.ncbi.nlm.nih.gov/pubmed/21981029. https://doi.org/10.1111/j.1399-5448.2011.00824.x.

Heo JW, Kim SW, Cho EH. Unsuccessful switch from insulin to sulfonylurea therapy in permanent neonatal diabetes mellitus due to an R201H mutation in the KCNJ11 gene: A case report. Diabetes Res Clin Pract. 2013;100(1):e1-2. https://www.ncbi.nlm.nih.gov/pubmed/23434183. https://doi.org/10.1016/j.diabres.2013.01.016.

Greeley SAW, Zielinski MC, Poudel A, et al. Preservation of reduced numbers of insulin-positive cells in sulfonylurea-unresponsive KCNJ11-related diabetes. J Clin Endocrinol Metab. 2017;102(1):1-5. https://www.ncbi.nlm.nih.gov/pubmed/27802092. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5413092. https://doi.org/10.1210/jc.2016-2826.

Bösenberg LH, van Zyl DG. The mechanism of action of oral antidiabetic drugs: A review of recent literature. JEMDSA. 2008;13(3):80-8. https://doi.org/10.1080/22201009.2008.10872177