Endocrine Abstracts

Background and aims: Most children with permanent neonatal diabetes (PNDM) have heterozygous mutations in KCNJ11, ABCC8 or INS genes if they have unrelated parents. Although homozygous mutations in GCK and ABCC8 have been described in the offspring of consanguineous parents the genetic aetiology in most of these cases remains unknown. We hypothesised that homozygous mutations in the INS gene could cause PNDM in these patients.<p class="ab...

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...

Nonautoimmune hyperthyroidism (NAH) inherited as an autosomal dominant trait can result from activating germline mutations in the thyrotropin receptor (TSHR) gene. Clinical features described include nonremitting thyrotoxicosis, absence of the features of autoimmune thyrotoxicosis, advanced bone age and increased growth velocity. We report a family with a heterozygous germline mutation of the TSHR gene resulting in the substitution of serine (AGC) by asparagine (AAC) at codon ...

Introduction: The MEN1 is inherited as autosomal dominant trait. In MEN 1 families a deletional mechanism of the regulatory gene appears to be the base of the syndrome.Case 1: 40-year-old lady presented with a two-day history of headaches, blurred vision and funny turns, culminating in loss of consciousness and a generalised tonic-clonic seizure. Her GCS was 3; she was intubated, ventilated and referred to ICU. U+Es normal, Calcium high, phosphate low, a...

Introduction: Hyperinsulinaemic hypoglycaemia (HH), characterized by unregulated insulin secretion from pancreatic β-cells, is an important cause of hypoglycaemia in children. Mutations in the KATP channel genes (ABCC8/KCNJ11) are the most common cause of congenital HH. The second common cause, hyperinsulinism hyperammonaemia (HIHA) syndrome caused by mutations in GLUD1 gene, is associated with elevated serum ammonia and protein sensitivity. W...

Locus-specific databases (LSDBs) have been recently developed in response to the increasing number of genetic changes reported in the human genome. LSDBs have been created for several genes implicated in endocrine syndromes, for example MEN1, VHL, RET, GNAS, PRKAR1A and the SDH subunits. Mutations in AIP are found in about 20% of familial isolated pituitary adenoma (FIPA) patients.The aim of this proj...

Background: It is often difficult to define the clinical relevance of a novel gene variant. In silico analyses of variants located close to exon–intron-junctions are utilised to predict the result of these basepair changes. We have previously identified two splice-site variants in AIP and confirmed the predicted changes for c.249G>T, p.G83AfsX15 and c.807C>T. We identified the c.469-2A>G heterozygous variant located at the end of intron-3 in a childhood...

Introduction: TNDM due to genetic aberrations at 6q24 is the commonest cause of diabetes presenting within the first week of life. TNDM predisposes to diabetes mellitus in later life. We report on the clinical presentation of the largest worldwide cohort of 6q24 TNDM cases.Results: 164 cases were analysed. The mean age of presentation was 8 days with a mode of 1 day and maximum age of presentation of 90 days. On average, babies recovered by 4.5 months wi...

Congenital hyperinsulinism (CHI) is a cause of severe and persistent hypoglycaemia due to unregulated insulin secretion from pancreatic β-cells. Mutations in the ABCC8 and KCNJ11 genes are the most common cause of medically unresponsive CHI. Histologically there are three major subgroups, focal, diffuse and atypical. The pathophysiology of focal CHI is complex and involves a two hit process with the patient firstly inheriting a paternal ABCC8/KCNJ11 m...

Background: Galactokinase catalyses the first committed step in galactose metabolism, the conversion of galactose to galactose-1-phosphate. Galactokinase deficiency is an extremely rare form of galactosaemia and the most frequent complication reported is cataracts. Congenital hyperinsulinism (CHI) is a cause of severe hypoglycaemia in the newborn period.Aims: To report the diagnostic pitfalls with bedside blood glucose testing in a neonate with combined ...