Longitudinal Auxological recovery in a cohort of children with Hyperinsulinaemic Hypoglycaemia

Background: Hypoglycaemia due to hyperinsulinism (HI) is the commonest cause of severe, recurrent hypoglycaemia in childhood. Cohort outcomes of HI remain to be described and whilst previous follow up studies have focused on neurodevelopmental outcomes, there is no information available on feeding and auxology. Aim: We aimed to describe HI outcomes for auxology, medications, feeding and neurodevelopmental in a cohort up to age 5 years. Method: We reviewed medical records for all patients with confirmed HI over a three-year period in a single centre to derive a longitudinal dataset. Results: Seventy patients were recruited to the study. Mean weight at birth was - 1.0 standard deviation scores (SDS) for age and sex, while mean height at 3 months was - 1.5 SDS. Both weight and height trended to the population median over the follow up period. Feeding difficulties were noted in 17% of patients at 3 months and this reduced to 3% by 5 years. At age 5 years, 11 patients (15%) had neurodevelopmental delay and of these only one was severe. Resolution of disease was predicted by lower maximum early diazoxide dose (p = 0.007) and being born SGA (p = 0.009). Conclusion: In a three-year cohort of HI patients followed up for 5 years, in spite of feeding difficulties and carbohydrate loading in early life, auxology parameters are normal in follow up. A lower than expected rate of neurodevelopmental delay could be attributed to prompt early treatment.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.The study was supported by the Northern Congenital Hyperinsulinism (NORCHI) charitable fund, by the Manchester Academic Health Sciences Centre and by The University of Manchester MRC Confidence in Concept (CiC) Award (MC_PC_18056). KEC was funded by a Research Councils UK Academic Fellowship (https://www.ukri.org/). SEF has a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (105636/Z/14/Z).published version, accepted versio

Focal Congenital Hyperinsulinism as a Cause for Sudden Infant Death.

Congenital hyperinsulinism (CHI) is the commonest cause of persistent and severe hypoglycemia in infancy due to unregulated insulin secretion from pancreatic β-cells. Prompt early diagnosis is important, as insulin reduces glucose supply to the brain, resulting in significant brain injury and risk of death. Histologically, CHI has focal and diffuse forms; in focal CHI, an inappropriate level of insulin is secreted from localized β-cell hyperplasia. We report a 4-month-old male infant, who presented with sudden illness and collapse without a recognized cause and died. Postmortem examination revealed pancreatic histopathology compatible with focal CHI. Immunofluoresence staining showed limited expression of p57kip2 β-cells reinforcing the diagnosis. Mutation testing for genes associated with CHI from DNA from the focal lesion was negative. This case highlights the recognition of focal CHI as a possible cause for sudden infant death. In children dying suddenly and unexpectedly, postmortem pancreatic sections should be carefully examined for focal CHI

Genotype and phenotype correlations in Iranian patients with hyperinsulinaemic hypoglycaemia.

Hyperinsulinaemic hypoglycaemia (HH) is a group of clinically and genetically heterogeneous disorders characterized by unregulated insulin secretion. Abnormalities in nine different genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, HNF4A, UCP2 and HNF1A) have been reported in HH, the most common being ABCC8 and KCNJ11. We describe the genetic aetiology and phenotype of Iranian patients with HH.This article is freely available via Open Access. Click on the 'Additional Link' above to access the full text

Conservatively treated Congenital Hyperinsulinism (CHI) due to K-ATP channel gene mutations: reducing severity over time.

Patients with Congenital Hyperinsulinism (CHI) due to mutations in K-ATP channel genes (K-ATP CHI) are increasingly treated by conservative medical therapy without pancreatic surgery. However, the natural history of medically treated K-ATP CHI has not been described; it is unclear if the severity of recessively and dominantly inherited K-ATP CHI reduces over time. We aimed to review variation in severity and outcomes in patients with K-ATP CHI treated by medical therapy.This article is freely available via Open Access. Click on Additional Link above to access the full-text via the publisher's website