hrp0094yb1.2 | Year of Paediatric Endocrinology 2 | ESPE2021

Antenatal and Neonatal Endocrinology

Hussain Khalid ,

I have chosen 3 manuscripts for my year book presentation on antenatal and neonatal endocrinology. The first manuscript describes the use of induced pluripotent stem cells (iPSCs) to study the genetic mechanisms of congenital hyperinsulinism (CHI). The derivation of iPSCs and their subsequent conversion to islet like clusters from a patient with diffuse CHI due to a homozygous mutation in the ABCC8 provides a unique opportunity to study the molecular basis of CHI and ...

hrp0082s8.1 | Novel Therapies in Paediatric Endocrinology | ESPE2014

Novel Therapies Used in the Management of Congenital Hyperinsulinism

Hussain Khalid

Congenital hyperinsulinism (CHI) is characterised by the dysregulation of insulin secretion leading to severe hyperinsulinaemic hypoglycaemia. Recent advances in molecular genetics have provided unique insights into understanding how insulin secretion becomes unregulated in CHI. Abnormalities in the genes ABCC8/KCNJ11 (encoding the two components SUR1/KIR6.2 of the pancreatic β-cell KATP channel respectively) is the most common genetic causes of CHI. Histologically there ...

hrp0086p2-p303 | Diabetes P2 | ESPE2016

Understanding the Molecular and Genetic Basis of Complex Syndromes of Diabetes Mellitus

Riachi Melissa , Hussain Khalid

Background: The two most commonly known types of Diabetes Mellitus (DM) are DM type 1 and DM type 2, characterized by insulin deficiency and insulin insensitivity, respectively. DM can also be associated with rare mutlisystemic syndromes such as Alstrom, Bardet-Biedl, Wolfram and pigmentary hypertrichosis insulin dependent diabetes (PHID) syndromes.Objectives: To understand the genetic and molecular basis of syndromic DM in a large cohort of patients.</p...

hrp0089p2-p018 | Adrenals and HPA Axis P2 | ESPE2018

A Novel Mutation in the MC2R Gene in a Two-year-old Boy with Adrenal Insufficiency

Al-Khawaga Sara , Hussain Khalid

Background: Melanocortin-2 receptor (MC2R) is a member of the G protein-coupled receptor family. MC2R is selectively activated by adrenocorticotropic hormone (ACTH); the binding of MC2R and ACTH activates the heterotrimeric G protein complex, and in turn stimulates steroidogenesis. Pathogenic variants in the MC2R gene result in glucocorticoid deficiency-1 (GCCD1), an autosomal recessive disorder in which unresponsiveness to ACTH leads to deficient secretion of cortisol and adr...

hrp0089p3-p254 | Growth &amp; Syndromes P3 | ESPE2018

Woodhouse-Sakati Syndrome: Clinical and Molecular Study on a Qatari Family with C2orf37 Gene Mutation

Al-Khawaga Sara , Khalifa Amal , Hussain Khalid

Background: Woodhouse-Sakati syndrome (WSS) is rare autosomal recessive condition characterized by progressive extrapyramidal signs, mental retardation, hypogonadism, alopecia, and diabetes mellitus. The age at disease onset, manifestation and severity of specific symptoms differs significantly among individuals with this syndrome and even among affected members of the same family. The gene C2orf37, which is responsible for WSS, located on chromosome 2q22.3-q35.<p class="a...

hrp0084p3-1066 | Hypo | ESPE2015

Congenital Hyperinsulinism in a Newborn with a Novel Paternally Inherited Heterozygous Mutation (p.E1517G) in the ABCC8 Gene

Elbarbary Nancy , Ellard Sian , Hussain Khalid

Background: Congenital hyperinsulinism (CHI), a clinically and genetically heterogeneous disease, is the most common cause of persistent hypoglycaemia in infancy.Case presentation: Here we describe an Egyptian male neonate first order of birth born to non-consanguineous healthy parents. At day 1 of age he presented with severe hypoglycemia and generalised seizures. At the time of hypoglycaemia (16 mg/dl) insulin and C-peptide levels were increased (insul...

hrp0092fc9.1 | Fetal, Neonatal Endocrinology and Metabolism (to include Hypoglycaemia) | ESPE2019

Using CRISPR/Cas9 Gene Editing to Study the Molecular Mechanisms of Congenital Hyperinsulinism (CHI)

Purushothaman Preetha , Walker Amy , Maeshima Ruhina , Hussain Khalid , Hart Stephen

Background: Congenital Hyperinsulinism(CHI) is characterized by the unregulated secretion of insulin in the presence of hypoglycaemia. The mutations in ABCC8 and KCNJ11, which encode the sulfonylurea receptor 1 (SUR1) and potassium inward-rectifying 6.2 (Kir6.2) subunits of ATP-sensitive potassium channel (K channel), are the most common identified cause of the condition. Defects in the HADH gene are responsible for SCHAD- HI, a rare form of the disease caused...

hrp0092p1-311 | Diabetes and Insulin (2) | ESPE2019

Optimisation of Transfection Methods Using DNA, RNA and Protein Formats for CRISPR Cas9 Mediated Gene Knock out in Beta-TC-6 Cells.

Purushothaman Preetha , Walker Amy , Hussain Khalid , Hart Stephen

Background: Beta-tumour cells (βTC) are a group of highly differentiated beta cell lines derived by expression of the SV40 T antigen (Tag) oncoprotein under control of the insulin promoter in transgenic mice. βTC-6 cells exhibit glucose stimulated insulin secretion which makes them a valuable tool in understanding the mechanisms that regulate insulin secretion.The CRISPR/Cas9 genome-editing platform is a versatile and pow...

hrp0086fc9.3 | Pathophysiology of Disorders of Insulin Secretion | ESPE2016

Gastrointestinal Dysmotility and Pancreatic Exocrine Insufficiency as Newly Recognised Possible Features in Two Siblings with Donohue Syndrome

Kostopoulou Eirini , Shah Pratik , Semple Robert , Ahmad Noman , Hussain Khalid

Background: Donohue syndrome is a rare congenital syndrome of insulin-resistance and abnormal glucose homeostasis, caused by mutations in the insulin receptor (INSR) gene. It is characterized by specific phenotypic and clinical features and the diagnosis is based on clinical, biochemical and genetic criteria.Case reports: We report two siblings with Donohue syndrome with typical dysmorphic features and multiple clinical and biochemical characteristics. G...

hrp0086lbp4 | (1) | ESPE2016

Sirolimus Precipitating Diabetes in a Patient with Congenital Hyperinsulinism due to Autosomal Dominant ABCC8 Mutation

Dastamani Antonia , Guemes Maria , Shah Pratik , Hussain Khalid

Background: Studies have suggested that sirolimus might be diabetogenic, mostly in kidney transplant recipients. Sirolimus has now been shown to be effective in the management of patients with congenital hyperinsulinism (CHI). However to date, there are no publications regarding the diabetogenic effect of Sirolimus in CHI patients.Objective and hypotheses: To report the first case of sirolimus precipitating diabetes in a CHI patient with known genetic mu...