hrp0098p1-167 | Growth and Syndromes 2 | ESPE2024

Familial Noonan Syndrome due to mutations in PTPN11 and PLOD1 genes

Chirayath Shiga , Mohammed Idris , Mohamadsalih Ghassan , Ben-Omran Tawfeg , Hussain Khalid

Introduction: Mutations in PTPN11 gene accounts for 50-60% of genetically identified patients with Noonan syndrome (NS). This report is of three siblings with familial NS due to mutation in PTPN11. Among the three, two of them have an additional mutation in PLOD1 gene and have normal height. The sibling who is shorter compared to the other two does not have this additional mutation. PLOD1 -related kyphoscoliotic Ehlers-Danlo...

hrp0098p2-128 | Fat, Metabolism and Obesity | ESPE2024

Identification and Functional Validation of Rare Missense Variants in PLXNA1 as a Candidate Gene for Severe Early-onset Obesity

Al-Barazenji Tara , Hammad Ayat , Mohammed Idris , Hussain Khalid , Al-Shafai Mashael

Background: Monogenic obesity (MO) is a rare form of obesity caused by mutations in a single gene, and characterized by being severe and with early onset. The leptin-melanocortin pathway is the main pathway controlling satiety and food intake. Genetic variants in this pathway have been implicated in MO with many being identified in consanguineous populations. Another group of neuronal proteins important in the development of neuronal circuits linked to energy ...

hrp0098fc6.1 | Fat, Metabolism and Obesity 1 | ESPE2024

Corneal Nerve Loss and regeneration after GLP-1 Therapy in Children with Simple and Monogenic Obesity

Gad Hoda , Dauleh Hajar , Chirayath Shiga , Amin Rasha , Mohamadsalih Ghassan , Pasha Maheen , Mohammed Idris , Al-Barazenji Tara , Khalifa Amel , Petrovski Goran , Hamdoun Elwaseila , Al Bureshad Khalid , Ibrahim Marwa , A. Malik Rayaz , Hussain Khalid

Background: Obesity is highly prevalent in the MENA region, especially in children and it has been associated with neurodegeneration. We have undertaken corneal confocal microscopy (CCM) to assess for evidence of neurodegeneration in children with simple obesity and monogenic obesity (MC4R gene mutation) and further assessed the effect of glucagon-like peptide 1 agonist (GLP-1) therapy on corneal nerve regeneration.Methods:</stro...

hrp0092p1-189 | Diabetes and Insulin (1) | ESPE2019

A Novel SLC2A2 Mutation Implicated in Fanconi Bickel Syndrome and Dysglycemia

Sharari Sanaa , Aouida Mustapha , Khan Faiyaz , Al-Khawaga Sara , Mohammed Idris , Haris Basma , Saraswathi Saras , Mundekkadan Shihab , Hussain1 Khalid

Background: Fanconi Bickel syndrome (FBS) is a rare form of glycogen storage disease (GSD) inherited in an autosomal recessive manner and caused by mutations in the SLC2A2 gene leading to the loss of GLUT2 glucose transporter expression. The disease is considered to be rare in which a little more than 100 cases have been reported in the literature. The SLC2A2 gene encodes for GLUT2, a low affinity facilitative glucose transporter expressed in critical tissues ...

hrp0089p1-p079 | Diabetes &amp; Insulin P1 | ESPE2018

A Novel SLCA16A1 Mutation in an Infant with Hypoglycemia and Severe Metabolic Ketoacidosis

Hasnah Reem , Al-Khawaga Sara , Saraswathi Saras , Haris Basma , Saeed Amira , Sharari Sanaa , Mohammed Idris , Hussain Khalid

Background: Recurrent episodes of ketoacidosis with or without hypoglycemia have been reported with homozygous or heterozygous mutations in the solute carrier family 16 member 1 (SLC16A1) gene. This gene encodes for the monocarboxylate transporter 1 (MCT-1) which plays a key role in lactate, pyruvate and ketone body transport.Objective(s): To describe the youngest patient with a novel SLC16A1 gene who presented with recurrent episodes of ketoacidosis and...

hrp0089p2-p281 | Growth &amp; Syndromes P2 | ESPE2018

A Novel Mutation in the SLC2A2 Gene in a 19-Year-Old Female with Diabetes Mellitus and Renal Tubular Acidosis: A Therapeutic Conundrum

Sharari Sanaa , Al-Khawaga Sara , Hasnah Reem , Saraswathi Saras , Haris Basma , Saeed Amira , Mohammed Idris , Malik Riyaz , Hussain Khalid

Background: Mutations in the SLC2A2 gene are implicated in Fanconi-Bickel syndrome (FBS). This is a rare form of glycogen storage disease (GSD) inherited in an autosomal recessive manner characterized by hepato-renal glycogen accumulation, impaired glucose and galactose utilization, and proximal renal tubular dysfunction. The world-wide frequency of Fanconi-Bickel syndrome is not known, though the disease is considered to be rare in which a little more that 100 cases ...

hrp0089p3-p238 | Growth &amp; Syndromes P3 | ESPE2018

Hypothyroidism and Growth Hormone (GH) Deficiency, a Spotlight on De Novo Chromosomal 20p11.2 Deletion

Mohammed Idris , Al-Khawaga Sara , Hannah Reem , Saraswathi Saras , Haris Basma , Saeed Amira , Shararri Sanaa , Hussain* Khalid

Background: There are few reports describing proximal deletions of chromosome 20p, making it difficult to predict the likely consequences of the deletion in this area. One report has described a proximal 20p11.2 deletion associated with panhypopituitarism, craniofacial dysmorphism, a small phallus with a semi bifid scrotum, and bilateral widely separated first and second toes. The only other report has demonstrated neurodevelopmental abnormalities associated with band 20p11.2 ...

hrp0086p1-p560 | Perinatal Endocrinology P1 | ESPE2016

Congenital Hyperinsulinism Due to Compound Heterozygous Mutation in ABCC8 and KCNJ11 GENES: 20 Years Experience of A National Referral Centre

Walton-Betancourth Sandra , Shah Pratik , Flanagan Sarah , Ellard Sian , Guemes Maria , Gilbert Clare , Silvera Shavel , Hussain Khalid

Background: Congenital hyperinsulinism (CHI) is a condition caused by dysregulated insulin secretion. Compound heterozygous mutations in ABCC8 or KCNJ11 genes account for approximately 13% of CHI mutations and have traditionally been associated with diffuse disease unresponsive to diazoxide.Objective and hypotheses: To analyse the clinical presentation and response to treatment of patients diagnosed with CHI due to compound heterozygous...

hrp0082p1-d1-175 | Perinatal and Neonatal Endocrinology | ESPE2014

The Role of mTORC1/RagGTPase and IGF1R/mTORC2/Akt Pathways and the Response of Diffuse Congenital Hyperinsulinism to Sirolimus

Senniappan Senthil , Tatevian Nina , Shah Pratik , Arya Ved Bhushan , Flanagan Sarah , Ellard Sian , Brown Robert , Hussain Khalid

Background: The gene expression microarray and morphoproteomics in diffuse congenital hyperinsulinism (CHI) revealed activation of the mammalian target of rapamycin (mTOR) pathway and the subsequent treatment of four diffuse CHI patients with sirolimus (mTOR inhibitor) avoided pancreatectomy.Objective and hypotheses: To further evaluate the mechanism of action of sirolimus by studying the expression of mTORC1/RagGTPase and IGF1R/mTORC2/Akt pathways in pa...

hrp0084fc9.4 | Beta cell disorders | ESPE2015

Novel Molecular Mechanisms of Congenital Hyperinsulinism due to Autosomal Dominant Mutations in ABCC8

Nessa Azizun , Aziz Qadeer , Thomas Alison , Harmer Stephen , Flanagan Sarah , Ellard Sian , Kapoor Ritika , Tinker Andrew , Hussain Khalid

Background: Dominant mutations in ABCC8 can cause congenital hyperinsulinism (CHI), which is characterised by unregulated insulin secretion.Objective and hypotheses: To understand the molecular basis of medically unresponsive CHI due to dominant ABCC8 mutations.Method: We investigated ten patients with diazoxide unresponsive CHI who required a near total pancreatectomy. DNA sequencing revealed seven dominant heter...