hrp0084p2-491 | Hypo | ESPE2015

Functional Analysis of Novel ABCC8 Mutations Found in Czech Patients with Congenital Hyperinsulinism

Rozenkova Klara , Dusatkova Petra , Dusatkova Lenka , Nessa Azizun , Obermannova Barbora , Kytnarova Jitka , Sumnik Zdenek , Lebl Jan , Hussain Khalid , Pruhova Stepanka

Background: Congenital Hyperinsulinism (CHI) is a heterogeneous genetically determined condition that is characterised by unregulated secretion of insulin from pancreatic β-cells. The most common and severe cases are caused by mutations in the ABCC8 gene encoding the SUR1 subunit of the KATP channel subunit. To assess the pathogenic effect of novel ABCC8 mutations we performed in-vitro functional studies.Objective and hy...

hrp0084p3-1067 | Hypo | ESPE2015

Discontinuation of Diazoxide Therapy in Children with Hyperinsulinaemic Hypoglycaemia with no Identified Genetic Aetiology: a Long-term Follow-up Study

Al Yahyaei Mouza , Shah Pratik , Guemes Maria , Gilbert Clare , Morgan Kate , Flanagan Sarah , Ellard Sian , Hussain Khalid

Background: Congenital hyperinsulinism (CHI) is a cause of severe persistent hypoglycaemia in children. Diazoxide is the first line medical therapy for CHI; however diazoxide is usually ineffective in CHI with KATP channel gene mutations. Patients with no mutations in the KATP channel genes do respond to therapy with diazoxide. There are no previous studies assessing how long diazoxide therapy is needed in those patients with no genetic aetiology identifi...

hrp0097rfc3.3 | Fat, metabolism and obesity 1 | ESPE2023

Early Corneal Nerve Loss in Children with Melanocortin 4 Receptor (MC4R) Gene Mutation Related Obesity

Gad Hoda , Dauleh Hajar , Pasha Maheen , Omer Idris , Al-Barazenji Tara , Alshafai Mashael , A. Hendaus Mohamed , A. Malik Rayaz , Hussain Khalid

Background: Obesity is highly prevalent worldwide, particularly in the MENA region. Whilst simple obesity has a variable genetic and environmental basis, syndromic and non-syndromic monogenic obesity has a strong genetic component. Melanocortin 4 receptor (MC4R) mutations are the commonest cause of monogenic obesity. MC4R also regulates neuropathic pain pathways via JNK signaling after nerve injury.Methods: Five children...

hrp0098p2-37 | Bone, Growth Plate and Mineral Metabolism | ESPE2024

Vosoritide Therapy in Children with Achondroplasia: Single-Center Experience

Amin Rasha , Ben-Omran Tawfeg , Khalifa Amel , Mohammed Elwaseila , Dauleh Hajar , Chirayath Shiga , Mohamadsalih Ghassan , A.Eyalawwad Ayah , Hussain Khalid

Background: Achondroplasia, the most prevalent skeletal dysplasia in children, is a multisystemic disease resulting from a common mutation in the fibroblast growth factor receptor 3 (FGFR3) gene. This mutation disrupts endochondral ossification, leading to disproportionate short stature. Historically, management has been primarily supportive due to the absence of targeted therapies. However, recent advancements have led to clinical trials for potential treatme...

hrp0089p2-p182 | Fetal, Neonatal Endocrinology and Metabolism P2 | ESPE2018

Clinical Characterstics, Genotype-Phenotype Correlations and Follow Up of Patients with Congenital Hyperinsulinaemic Hypoglycaemia; Single Center Experience from a Southeastern City of Turkey

Ozbek Mehmet Nuri , Demirbilek Huseyin , Haliloglu Belma , Demiral Meliha , Baran Riza Taner , Ellard Sian , Houghton Jayne , Flanagan Sarah E , Hussain Khalid

Objective: Congenital Hyperinsulinism (CHI) is a clinically, genetically and histologically heterogenous diesease. In recent years substantial developements have been observed in the genetics, imaging techniques and treatment options. We herein present the clinical characteristics, genetics and follow-up of 31 CHI patients from a single paediatric endocrine center with a particular emphasis on the new treatment options.Patients and method: Clinical chara...

hrp0086fc3.4 | Pituitary | ESPE2016

A Novel Mutation in Eukaryotic Translation Initiation Factor 2 Subunit 3 (EIF2S3) is Associated with X-Linked Hypopituitarism and Glucose Dysregulation

Gregory Louise C. , Williams Hywel , Rahman Sophia , Ferreira Carolina B. , Alatzoglou Kyriaki S. , Kapoor Ritika R. , Hussain Khalid , Gaston-Massuet Carles , Kelberman Daniel , Qasim Waseem , Dattani Mehul T.

Background: A mutation in EIF2S3 (NM_001415; Xp22.11) was previously associated with microcephaly and developmental delay in a single pedigree. EIF2S3 encodes the eukaryotic translation initiation factor 2 subunit 3 (eIF2γ), the largest of three EIF2 subunits. EIF2 initiates protein synthesis by forming a ternary complex with GTP and initiator methionyl-tRNA which then binds to the 40S ribosomal subunit, enabling scanning of mRNA from the 5′ end to...

hrp0082fc9.4 | Beta cells | ESPE2014

Clinical Characteristics and Molecular Genetics Analysis of 20 Patients with Neonatal Diabetes Mellitus from a Single Centre of the South-Eastern Region of Turkey

Demirbilek Huseyin , Arya Ved Bhushan , Nuri Ozbek Mehmet , Houghton Jayne , Baran Riza Taner , Tekkes Selahattin , Mackay Deborah , Flanagan Sarah E , Ellard Sian , Hussain Khalid

Background: Neonatal diabetes mellitus (NDM), either transient (TNDM) or permanent (PNDM), is a rare form of monogenic diabetes, and usually presents in the first 6 months of life.Objective and Hypotheses: To describe the clinical characteristics and molecular genetics of a large Turkish cohort of NDM from a single centre.Method: NDM patients presenting to Diyarbakır Children State Hospital between 2010 and 2013 were prospecti...

hrp0082p1-d1-182 | Perinatal and Neonatal Endocrinology | ESPE2014

Clinical and Histological Heterogeneity of Congenital Hyperinsulinism Due to Paternally Inherited Heterozygous ABCC8/KCNJ11 Mutations

Arya Ved Bhushan , Guemes Maria , Nessa Azizun , Alam Syeda , Shah Pratik , Gilbert Clare , Senniappan Senthil , Flanagan Sarah E , Ellard Sian , Hussain Khalid

Context: Congenital hyperinsulinism (CHI) has two main histological types – diffuse and focal. Diffuse CHI is due to recessive or dominant mutations in ABCC8/KCNJ11. Focal disease is due to somatic maternal allele loss of 11p15 in pancreatic β-cells along with paternally inherited germline ABCC8/KCNJ11 mutation. Fluorine-18 L-3, 4-dihydroxyphenylalanine positron emission tomography computerized tomography (18F DOPA–PET...

hrp0082p2-d1-324 | Diabetes | ESPE2014

Two Novel Homozygous Mutations in WFS1 Gene in Two Turkish Families with Mild Phenotypic Expression of Wolfram Syndrome

Sherif Maha , Demirbilek Huseyin , Cayir Atilla , Ozbek Mehmet Nuri , Baran Riza Taner , Cebeci Ayse Nurcan , Tahir Sophia , Rahman Sofia , Dattani Mehul , Hussain Khalid

Background: Wolfram syndrome (WS or DIDMOAD) is a rare (prevalence of 1/770,000) autosomal recessive multi-systemic neurodegenerative disease, characterized by non-autoimmune diabetes mellitus (DM) and optic atrophy. Additional features include diabetes insipidus (DI), sensorineural deafness, urinary tract abnormalities, ataxia, psychiatric illness, and other endocrine disturbances leading to death in mid-adulthood. This syndrome is caused by recessive mutations in the wolfram...

hrp0084fc3.3 | Diabetes | ESPE2015

Clinical Characteristics and Molecular Genetic Analysis of Six Patients with Pancreas Aplasia and Neonatal Diabetes: Predominance of PTF1A-Enhancer Mutations

Raile Klemens , Gong Maolian , Spagnoli Francesca , Chen Wei , Hummel Oliver , Darendeliler Feiza , Bober Ece , Abaci Ayhan , Krill Winfried , Thiel Susanne , Kuhnen Peter , Hussain Khalid

Background: Pancreas aplasia (PA) and neonatal diabetes mellitus (NDM) syndrome is a rare disease that usually presents in the 1st months of life.Objective and hypotheses: We aimed to characterize molecular genetic defects in a cohort of six NDM/PA patients with up-to-date unknown pathogenesis with optimum genetic testing.Method: As part of our ESPE-RU-project ‘Understanding the molecular basis of diabetes mellitus associated ...