ESPE Abstracts

Background: Neonatal diabetes (ND) is a rare monogenic form of diabetes presenting within the first six months of life. The most frequent causes include mutations in KCNJ11, ABCC8 and insulin genes, but up to 40% of patients remain without a molecular genetic diagnosis.Case presentation: Case 1: a female newborn of non-consanguineous parents, born at 35 weeks, SGA. She presented with hyperglycemia at second day of life...

Background: The gene expression microarray and morphoproteomics in diffuse congenital hyperinsulinism (CHI) revealed activation of the mammalian target of rapamycin (mTOR) pathway and the subsequent treatment of four diffuse CHI patients with sirolimus (mTOR inhibitor) avoided pancreatectomy.Objective and hypotheses: To further evaluate the mechanism of action of sirolimus by studying the expression of mTORC1/RagGTPase and IGF1R/mTORC2/Akt pathways in pa...

Background: Dominant mutations in ABCC8 can cause congenital hyperinsulinism (CHI), which is characterised by unregulated insulin secretion.Objective and hypotheses: To understand the molecular basis of medically unresponsive CHI due to dominant ABCC8 mutations.Method: We investigated ten patients with diazoxide unresponsive CHI who required a near total pancreatectomy. DNA sequencing revealed seven dominant heter...

Background: Hyperinsulinaemic hypoglycaemia (HH) can be transient or permanent. Transient HH (spontaneous resolution of HH within few weeks) is associated with intrauterine growth restriction, maternal diabetes, erythroblastosis fetalis etc. Transient HH has not been reported with ABCC8/KCNJ11 mutations, which are the commonest cause of HH.Aim: Molecular characterisation of a novel ABCC8 mutation associated with a transient HH phenotype seen in a family ...

Background: Congenital hyperinsulinism (CHI) is a cause of severe persistent hypoglycaemia in children. Diazoxide is the first line medical therapy for CHI; however diazoxide is usually ineffective in CHI with KATP channel gene mutations. Patients with no mutations in the KATP channel genes do respond to therapy with diazoxide. There are no previous studies assessing how long diazoxide therapy is needed in those patients with no genetic aetiology identifi...

Background: The efficacy of growth hormone (GH) treatment in short, healthy children diagnosed with growth hormone deficiency (GHD) or those meeting the criteria of idiopathic short stature (ISS) suggest that an overlap exists between these two conditions. Although flawed and inconsistent, growth hormone stimulation tests (GHST) are the key diagnostic tool differentiating between GHD and ISS affecting clinical decisions such as treatment eligibility and dose.<...

Introduction: Congenital hyperinsulinism (CHI) is a rare condition often caused by variants in genes that regulate insulin production. Among the 30 genes identified, CACNA1D, which encodes L-type calcium channels in various cells, is a rare cause. Variants in CACNA1D lead to a multisystem disorder characterized by developmental delay, intellectual disability, autism, hypotonia, seizures, primary aldosteronism, CHI, hearing loss, visual issues...

We report a term male with diazoxide-unresponsive congenital hyperinsulinism (CHI) (spontaneous conception, non-consanguineous, no family history). The patient did not have macroglossia, exomphalos or lateralised overgrowth (cardinal Beckwith-Wiedemann spectrum (BWSp) features) (1). There was no polyhydramnios, macrosomia, facial naevus simplex, ear creases/pits, diastasis recti or nephromegaly/hepatomegaly (suggestive BWSp features) (1).A targeted massi...

Introduction: Hyperinsulinaemic Hypoglycaemia (HH) is one of the commonest causes of hypoglycaemia in infancy. It is characterised by hypoketotic, hypofattyacidaemic and hyperinsulinaemic hypoglycaemia. The molecular basis of HH includes defects in pathways that regulate insulin release; to date, 12 genes have been associated with monogenic forms of HH (ABCC8, KCNJ11, GLUD1, GCK, HADH1, UCP2, MCT1, HNF4A, HNF1A, HK1, PGM1, PMM2). However, no genetic aetiology has been...

Background: GLIS3 is a transcription factor involved in the development of pancreatic β-cells, the thyroid, eyes, liver and kidneys. In the pancreas, GLIS3 is expressed at various stages of ductal and endocrine cell development, and is a critical regulator of β-cell development and insulin expression. Mutations in GLIS3 have been recently described as a rare cause of neonatal diabetes and congenital hypothyroidism (CH), reported in only 20 ...