ESPE Abstracts (2016) 86 P-P1-235

The Genetic Causes and Phenotypic Characteristics of Egyptian Patients with Neonatal Diabetes Mellitus

Rasha Elkaffasa,b, Noha Musac, Elisa De Francod, Hanan A Madanib, Yomna Shaalanc, Rania M.H. El-Kaffasc, Mona Hassanc, Mona Hafezc, Badawy El Kholib, Sarah E Flanagand, Sian Ellardd & Khalid Hussaina

aInstitute of Child Health, UCL, London, UK; bChemical Pathology Department, Cairo University, Cairo, Egypt; cPediatrics Department, Cairo University, Cairo, Egypt; dInstitute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK

Background: Neonatal Diabetes Mellitus (NDM) is a rare form of monogenic diabetes that typically presents during the first 6 months of life. Its prevalence is about 1:100 000 live births; however it may rise up to 1:29 000 in highly consanguineous populations. Mutations in 22 different genes are reported; with the most common cause being potassium channel subunit gene (KCNJ11/ABCC8) mutations. However, causative mutations among consanguineous populations seem to differ. Studies on NDM in these populations are still limited.

Objective and hypotheses: Our aim was to identify the causative mutations among a group of Egyptian patients with NDM and to describe their clinical phenotypes.

Method: The study was performed on 16 Egyptian patients with NDM onset at or before the age of 6 months who attended the Diabetic Endocrine and Metabolic Paediatric Unit (DEMPU) at the Children’s Hospital of Cairo University in Egypt. Sanger sequencing was undertaken for the common causative genes (KCNJ11, ABCC8, INS and EIF2AK3) as a first test, followed by targeted next generation sequencing for the remaining known genes.

Results: Mean age of onset of NDM was 2.6 months, 10/16 were born from consanguineous parents and 11/16 presented with diabetic ketoacidosis. Eight mutations have been detected so far; only 4/16 patients had potassium channel gene mutations: two in KCNJ11 and two in ABCC8. One homozygous GCK gene mutation was detected. A chromosome 6q24 methylation defect was detected in one patient with transient NDM, a homozygous EIF2AK3 mutation was detected in one patient with Wolcott Rallison syndrome and a homozygous SLC19A2 mutation was detected in a patient with Thiamine Responsive Megaloblasic Anaemia syndrome.

Conclusion: Potassium channel subunit gene mutations are not common among the studied group. Further studies are required to determine common mutations among the Egyptian population.