ESPE Abstracts

Background: Little is known about the prevalence of neonatal hypoglycaemia in the absence of known risk factors, nor its associated neurodevelopmental outcomes. Neurological harm from hyperinsulinism induced hypoglycaemia (HH) may be due to the direct effect of hypoglycaemia as well as its sequelae, such as seizures or apnoeas, leading to secondary insults such as hypoxic brain injury. With our case series we highlight such risks and propose changes to support early diagnosis.

Methods: This study is a collaboration between two quaternary paediatric endocrinology centres in the UK. It comprises a literature review of congenital hyperinsulinism and guidelines on neonatal hypoglycaemia provided by national bodies. We present a case series reporting the clinical, biochemical, genetic, radiological, and neurodevelopmental findings of five neonates from two regional centres who, despite having no identifiable risk factors, presented with hyperinsulinaemic hypoglycaemia. Signed informed consent was obtained from the caregivers of patients involved in this case series.

Results: Each case followed the same presenting pattern of poor feeding, reduced tone and later, seizures. All five cases were treated with a combination of diazoxide and chlorothiazide. MRI findings were consistent across cases, showing restricted diffusion in the posterior cortical region and in particular, the occipital lobe. Further restriction was found in 4/5 patients in the precentral gyrus, temporal and frontal lobes. Genetic analysis via TGNS and Sanger sequencing showed no pathogenic variants of genes associated with hyperinsulinism. Development was assessed in 4/5 patients; two have severe global developmental delays, one has abnormal motor skills, and one demonstrates normal development. Two cases developed epilepsy. The unassessed case is at high risk of visual impairment, cerebral palsy, and epilepsy.

Conclusion: Guidelines on the identification of neonatal hypoglycaemia emphasise identification in neonates with risk factors. We recommend that healthcare providers remain vigilant to the signs and symptoms of hypoglycaemia in all neonates through having a low threshold for checking blood glucose and referring to specialist hospital teams if concerned. We propose strategies to increase awareness on the signs of hypoglycaemia (especially abnormal feeding). Costs of a lower clinical threshold for checking blood glucose may be offset by avoiding large medicolegal fees and long-term health costs incurred by a late diagnosis of HH. We recommend the re-evaluation of patients to identify genetic causes of hyperinsulinism and support research into the prevalence of this condition.