title: Genetic characteristics, clinical spectrum, and incidence of neonatal diabetes in the Emirate of AbuDhabi, United Arab Emirates.
abstract: Neonatal diabetes mellitus (NDM) can be transient (TNDM) or permanent (PNDM). Data on NDM from the Gulf region are limited to few studies on PNDM.The objective of this study was to describe the genetic and clinical spectrum of NDM and estimate its incidence in AbuDhabi, capital of the United Arab Emirate (UAE). Patients were identified from the pediatric diabetes clinics and sequencing of known NDM genes was conducted in all families. Twenty-five patients were identified. Incidence during 1985-2013 was 1:29,241 Live births. Twenty-three out of twenty-five had PNDM (incidence 1:31,900) and 2/25 had TNDM (incidence 1:350,903). Eleven out of twenty-five had extra-pancreatic features and three had pancreatic aplasia. The genetic cause was detected in 21/25 (84%). Of the PNDM patients, nine had recessive EIF2AK3 mutations, six had homozygous INS mutations, two with deletion of the PTF1A enhancer, one was heterozygous for KCNJ11 mutation, one harboured a novel ABCC8 variant, and 4/21 without mutations in all known PNDM genes. One TNDM patient had a 6q24 methylation defect and another was homozygous for the INS c-331C>G mutation. This mutation also caused permanent diabetes with variable age of onset from birth to 18 years. The parents of a child with Wolcott-Rallison syndrome had a healthy girl following pre-implantation genetic diagnosis. The child with KCNJ11 mutation was successfully switched from insulin to oral sulphonylurea. The incidence of PNDM in Abu Dhabi is among the highest in the world and its spectrum is different from Europe and USA. In our cohort, genetic testing has significant implications for the clinical management.
authors.affiliation: Department of Pediatric Endocrinology, Mafraq Hospital, AbuDhabi, United Arab Emirates.
authors.forename: Asma
authors.initials: A
authors.lastname: Deeb
authors.affiliation: Department of Pediatric, Prince Mohamed bin Abdulaziz Hospital, Madinah, Saudi Arabia.
authors.forename: Abdelhadi
authors.initials: A
authors.lastname: Habeb
authors.affiliation: Department of Endocrine, Tawam Hospital, Al Ain, United Arab Emirates.
authors.forename: Walid
authors.initials: W
authors.lastname: Kaplan
authors.affiliation: Department of Pediatric Endocrinology, Mafraq Hospital, AbuDhabi, United Arab Emirates.
authors.forename: Salima
authors.initials: S
authors.lastname: Attia
authors.affiliation: Department of Endocrine, Tawam Hospital, Al Ain, United Arab Emirates.
authors.forename: Suha
authors.initials: S
authors.lastname: Hadi
authors.affiliation: Imperial College London Diabetes Center, Al Ain, United Arab Emirates.
authors.forename: Amani
authors.initials: A
authors.lastname: Osman
authors.affiliation: Department of Pediatric Endocrinology, Shaikh Khalifa Medical Center, AbuDhabi, United Arab Emirates.
authors.forename: Jamal
authors.initials: J
authors.lastname: Al-Jubeh
authors.affiliation: Department of Molecular Genetics, Institute of Biomedical and Clinical Science, Peninsula Medical School, University of Exeter, Exeter, United Kingdom.
authors.forename: Sarah
authors.initials: S
authors.lastname: Flanagan
authors.affiliation: Department of Molecular Genetics, Institute of Biomedical and Clinical Science, Peninsula Medical School, University of Exeter, Exeter, United Kingdom.
authors.forename: Elisa
authors.initials: E
authors.lastname: DeFranco
authors.affiliation: Department of Molecular Genetics, Institute of Biomedical and Clinical Science, Peninsula Medical School, University of Exeter, Exeter, United Kingdom.
authors.forename: Sian
authors.initials: S
authors.lastname: Ellard
mesh_terms: D000293:Adolescent; D002648:Child; D002896:Chromosomes, Human, Pair 6; D003241:Consanguinity; D003920:Diabetes Mellitus / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D005820:Genetic Testing; D006801:Humans; D015994:Incidence; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D007328:Insulin / Q000235:genetics*; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D064233:Sulfonylurea Receptors / Q000235:genetics*; D014479:United Arab Emirates / Q000453:epidemiology; D019892:eIF-2 Kinase / Q000235:genetics*; D000099161:Kcnj11 Channel
chemical_list: D007328:Insulin; D024661:Potassium Channels, Inwardly Rectifying; D064233:Sulfonylurea Receptors; D019892:eIF-2 Kinase; D000099161:Kcnj11 Channel; C577507:ABCC8 protein, human; C460640:EIF2AK3 protein, human
keywords: KATP; Wolcott-Rallison syndrome; insulin gene; neonatal diabetes