Endocrine Abstracts

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...

IntroductionFamilial hypocalciuric hypercalcemia (FHH) is an autosomal dominant trait comprising hypercalcemia, hypophosphatemia and an unusually low renal clearance of calcium. The vast majority of FHH is caused by loss-of-function mutations in the gene CASR, which codes for the calcium-sensing receptor (CASR). CASR is a G-protein coupled membrane receptor expressed in the parathyroid glands and the kidneys, among other tissues. It is generally asymptom...

The activity of certain hypothalamic neuronal populations is altered by changes in glucose. in-vitro studies have identified several glucose-sensitive neuronal populations in hypothalamic regions controlling energy homeostasis. Subsets of orexigenic arcuate nucleus Neuropeptide Y (NPY)-releasing neurones are known to be glucose responsive. These neurones may allow glucose to influence appetite. Cocaine and amphetamine regulated transcript (CART) is a neurotransmitter ab...

In Ireland, we are devolving management of diabetes to primary care. Recent studies highlight the importance of early glycemic (metabolic memory) & multifactorial control. Our hospital‘new’patient waiting lists average 18 months and for ‘best practice’, this is “time lost”. We established a pilot program for a rapid assessment to reduce waiting times and ensure specialist input. This is a retrospective review of our 50 patients thus far. 30% w...

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...

We describe the case of a 22-year-old South Asian male presenting to Endocrine Services with morbid obesity (BMI>50), sexual immaturity and agoraphobia. Born at full term following an uncomplicated pregnancy, he reached all developmental milestones appropriately. His problems began aged 15 after witnessing a murder, with reactive depression and hyperphagia. By the age of 18, he weighed over 140 kg, had poor self-image and suicidal ideation. He was managed initially by seve...