Endocrine Abstracts

Background: Congenital hyperinsulinism (CHI) is the commonest cause of persistent hypoglycaemia and is due to the unregulated secretion of insulin from the pancreatic beta-cells. The role of gut hormones and dipeptidyl peptidase-4 (DPP-4) is currently unknown in patients with CHI.Aims: To evaluate the expression pattern of DPP-4 in focal and diffuse CHI.Method: Using intra-operative formalin-fixed paraffin embedded (FFPE) pancreati...

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.Aims: The aim is to use the novel CRISPR/Cas9 gene editing technique to create a KO...

Introduction: Mutations in SLC29A3 lead to PHID and H syndromes, familial Rosai Dorfman Disease and Histiocytosis-lymphadenopathy plus syndrome. PHID syndrome is associated with short stature, pubertal delay, endocrine and exocrine pancreatic insufficiency. We report a new association of PHID syndrome with severe systemic inflammation, scleroderma-like changes and cardiomyopathy.Case report: A 12-year-old girl with PHID syndrome presented with shortness ...

Introduction: Beckwith-Wiedemann syndrome (BWS) is characterized by hyperinsulinaemic hypoglycaemia (HH), overgrowth, tumour predisposition and congenital malformations. Commonly, BWS is caused by epigenetic or genomic alterations, which disrupt genes in one or both of the two imprinted domains on chromosome 11p15.5. Rarely (~1%), paternally inherited duplications of 11p15 can result in BWS phenotype. We describe the first case of BWS associated with a paternally inherited dup...

Beckwith–Wiedemann syndrome (BWS) is an overgrowth syndrome caused by multiple epigenetic and genetic changes. It is due to genetic and epigenetic mechanisms affecting the balance of imprinted genes on chromosome 11p15.5. This region has two imprinted control regions, ICR1 and ICR2. ICR1 contains the genes H19 and IGF2 genes with H19 being maternally expressed and IGF2 paternally expressed. ICR2 contains the KCNQ1, KCNQ1OT1, and CDKN1C genes. Hypomethylation of KvDMR1 (an...

Background: Pigmented hypertrichotic dermatosis with insulin-dependent diabetes (PHID) syndrome is an autosomal recessive disorder due mutations in SLC29A3. SLC29A3 encodes for an equilibrative nucleoside transporter 3 (ENT 3). A hallmark of PHID syndrome is the chronic inflammation characterised by the persistently raised erythrocyte sedimentation rate and C-reactive protein. A key pathway involved in triggering inflammation is the nuclear factor kappa β (N...

Congenital hyperinsulinism (CHI) is a clinically and genetically heterogeneous disease. The clinical heterogeneity may range from mild subtle hypoglycaemia to severe life threatening hypoglycaemia. The commonest genetic cause of congenital hyperinsulinism are mutations in the genes ABCC8 and KCNJ11 encoding the two subunits (SUR1 and Kir6.2 respectively) of the pancreatic β-cell KATP channel. In the Ashkenazi Jewish population two founder mutation...

Background: The CRISPR/Cas9 genome-editing platform is a powerful technology to create genetically engineered cells and organisms. However, the success of CRISPR genome editing experiments is limited by the intracellular delivery and expression of Cas9 endonuclease protein and guide RNA (gRNA). Beta-tumour cells (βTC-6), derived from transgenic mice, exhibit glucose stimulated insulin secretion which makes them a valuable tool in understanding the mechanisms that regulate...

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 by the disruptio...

Background: Children with hyperinsulinaemic hypoglycaemia (HH) are at a high risk of brain injury, while children with ketotic hypoglycaemia (KH) are believed to be neurologically normal. Hippocampus is known to be susceptible to hypoglycaemia, and is one of the key structures in the memory system. Our objective was to ascertain if children with HH sustain greater hippocampal injury and memory deficits in comparison to children with KH.Methods: Twenty on...