ESPE Abstracts

Introduction: Mendelian diseases are rare individually but collectively are estimated to affect more than 5% of global population with more than 6000 different rare phenotypes including monogenic forms of diabetes. The proportion of individuals who possess a particular genotype and exhibit the expected phenotype is defined as the penetrance of that genotype. If everyone with the genotype presents with clinical symptoms by a particular age, then it is said to b...

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 ...

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 ...

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...

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...

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...

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...

Background: Congenial Leptin deficiency (CLD) manifests as severe obesity, hyperphagia, and metabolic complications. While Metroleptin is the treatment of choice, its cost makes it inaccessible for many. We present two sisters, aged 14 and 7, diagnosed with CLD, who had significant improvement with the glucagon-like peptide-1 (GLP-1) receptor agonist, Semaglutide. Both experienced notable reduction in body weight and metabolic markers with Semaglutide, highlig...

Background: Congenital leptin deficiency (CLD) is an extremely rare condition due to homozygous pathogenic mutations in the leptin (LEP) gene. The clinical manifestation of patients with CLD is severe early-onset obesity and hyperphagia. Most patients with pathogenic homozygous leptin gene mutations have low or undetectable leptin levels, whereas few cases show high bio-inactive circulating leptin levels. To date, around 20 variants in the LEP gene have been d...

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...