Focal Congenital Hyperinsulinism as a Cause for Sudden Infant Death

Abstract

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 p57 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.

Hyperinsulinemic hypoglycemia in children and adolescents: Recent advances in understanding of pathophysiology and management

“…The risk of permanent brain injury in infants with HH continues to be as high as 25-50% due to delays in diagnosis and inadequate treatment. Despite advances in genetics, improved modes of investigation, novel management options and abrigding pediatric and adult followup in holistic multidisciplinary transition clinics, significant morbidity and mortality is still a major issue in children and young adults with HH [3][4][5].…”

A reliable and automated synthesis of 6-[18F]fluoro-L-DOPA and the clinical application on the imaging of congenital hyperinsulinism of infants

“…Congenital hyperinsulinism (CHI), the inappropriate secretion of insulin by the pancreatic β-cells, is among the major causes for severe hypoglycemia in infants [28]. Rapid diagnosis of CHI is of high importance because the presence of abnormal level of insulin may lead to seizure and signi cant brain damage or even death [29]. PET imaging with 6-[ 18 F]Fluoro-L-DOPA as radiotracer has been reported as an important approach to diagnose CHI with high accuracy [30][31][32].…”

Clinical Diversity in Focal Congenital Hyperinsulinism in Infancy Correlates With Histological Heterogeneity of Islet Cell Lesions

“…Indeed, since loss of heterozygosity can occur at any time during embryogenesis, our data show that CHI-F is underpinned by heterogeneity in both structure and organization of the lesion domain. We found that in ~30% of patients, the organizational aspects of focal lesion were poor and the limits of the endocrine cell mass were difficult to define ( 5 ). This form of CHI-F has been alluded too by others in both large cohorts of patients or unusual case reports without reference to clinical severity of pathobiology ( 27 , 28 , 34 – 37 ).…”

“…Twenty four patients were aged between 1 and 19 months at the time of surgery, Table 1 . One subject was not diagnosed with CHI-F until after death at 4 months of age ( 5 ). Pancreatic surgery was performed for alleviation of sustained hypoglycaemia in patients with poor or inappropriate responses to medical therapy, Table 2 .…”