Endocrine Abstracts

Background: PHID is a novel syndrome caused by mutations in SLC29A3, which encodes for the nucleoside transporter protein hENT3. It is associated with multiple endocrine manifestations including severe short stature, pubertal delay and pancreatic exocrine insufficiency. Mutations in SLC29A3 have also been linked to H syndrome and familial Rosai Dorfman Disease (RDD). A key feature of these syndromes is persistent inflammation. Currently there is no treatment for ...

Background: HADH encodes for the enzyme 3-hydroxyacyl-coenzyme A dehydrogenase (HADH) and catalyses the penultimate reaction in the beta-oxidation of fatty acids. Mutations in the HADH gene have recently been described to cause protein sensitive hyperinsulinaemic hypoglycaemia (HH). Protein sensitive HH (specifically leucine sensitivity), is also associated with the hyperinsulinism-hyperammonaemia syndrome (HI/HA syndrome) caused by activating mutations of GLUD1 ...

Introduction: Obesity is one of the biggest health challenges we currently face. Obesity results from imbalance of energy consumption and expenditure. Genetic studies on monogenic forms of obesity and Genome Wide Association studies have revealed neuronal mechanisms of genesis of obesity and/or leanness. We report a novel disorder of increased energy expenditure with severe failure to gain weight and increased brown fat.Case report: The proband is a whit...

Background: Hyperinsulinism–hyperammonaemia (HI/HA) syndrome is caused by gain of function mutations in the GLUD1 gene. Patients present with recurrent hyperinsulinaemic hypoglycaemia (HH) together with asymptomatic, persistent elevation of plasma ammonia levels. Leucine sensitivity is an important feature of this condition.Objectives: The aim of this study was to understand the genotype phenotype correlations in patients with HH due to GLUD1 mutati...

Hyperinsulinism in Infancy (HI) is a potentially-lethal condition of neonates and during early childhood. For many years the pathophysiology of this disorder was unknown. Recent advances in genetics, histopathology and molecule physiology have now revealed the causes of HI in a large cohort of patients. This review focuses upon the relationship between the basis of HI and current treatment options. From defects in ion channel subunit genes to lesions in the control of pancreat...

ATP-evoked signalling events are known to promote release of insulin from pancreatic beta-cells in a Ca2+-dependent manner. In rodent beta-cells and insulin-secreting cell lines, this is mediated by purinergic receptors and there is evidence for the involvement of both P2X and P2Y subtypes. Here,we have used human insulin-secreting cells to examine the expression of purinoceptors in control and disease tissue. Intact islets and isolated beta-cells were obtained from...

Congenital hyperinsulinism (CHI) is characterised by unregulated insulin secretion from pancreatic β-cells. The most severe forms are associated with defects in SUR1 and Kir6.2 (encoded by ABCC8 and KCNJ11), which form KATP channels in β-cells. Diazoxide therapy often fails in the treatment of CHI and may be due to reduced cell surface expression of KATP channels. We investigated methods to increase surface expression of KATP<...

Hyperinsulinism in Infancy (HI) is the most common cause of recurrent or persistent hypoglycaemia in early childhood, and manifests as either diffuse abnormalities of pancreatic beta-cell function (Di-HI), or focal adenomatous hyperplasia of beta-cells (Fo-HI). Di-HI is caused by defects in KATP channel genes ABCC8 (SUR1) or KCNJ11 (Kir6.2). Fo-HI arises from somatic loss of maternal heterozygosity resulting in the expression of paternally-derived mutation(s) in SUR1 or Kir6.2...