ESPE Abstracts

Hyperinsulinism is a common cause of persistent hypoglycemia beyond infancy. Mutations in the ABCC8/KCNJ11 genes are the most common aetiology of congenital hyperinsulinism (CHI), leading to KATP channel mutation. This results in an inappropriate insulin secretion irrespective of hypoglycaemia. This is a cross-sectional study of the patients attending the paediatric endocrinology unit at the National Centre for Child Health & Development (NCCHD), Tokyo, Japan from March 2022 to March 2023. Only the patients who had a genetic study done were included in this study. The aim of our study is to analyze the patient characteristics of ABCC8/KCNJ11 genetic mutations and the long-term outcome. There was a total of 31 patients, with 17 (54.8%) patients who were male. The mean age was 10.56 (2.30 – 31.75) years old and the majority of the patients were of Japanese ethnicity, 29 (93.5%). The mean birth weight was 3.53 kg (1.98 – 5.12). There was a total of 16 (51.6%) patients were positive for ABCC8/KCNJ11 mutations. Among the other positive genetic mutation detected in our cohort includes 2 (6.5%) GLUD1 mutation, UPD11 mutation 4 (12.9%), KMT2D 1 (3.2%) while others were negative 8 (25.8%). Among the patients with ABCC8/KCNJ11 mutations – 9(56.3%) were male, and 14 (87.5%) were Japanese. Among the patients who were born with a birth weight of 4 kg and above, 8 (72.7%) of the patients had ABCC8/KCNJ11 mutation. F-DOPA-PET scan was performed in 13 (81.3%) patients with ABCC8/KCNJ11 mutations. The imaging findings of these patients were diffuse in 4 (25.0%) patients. Others had localized findings including 4 (25.0%) in body and tail, 1 (6.3%) in the focal body, 1 (6.3%) in the focal head, and 1 (6.3%) patient with multifocal distribution in the pancreas. Among the ABCC8/KCNJ11 patients, 9 (56.3%) underwent pancreatectomy and the rest were managed with medications only. Currently, 10 (62.5%) of the ABCC8/KCNJ11 patients still have persistent disease. With regards to long-term complications, among the patients with ABCC8/KCNJ11 mutation, 2 (12.5%) patients had neurological complications, 1 (100%) has pancreatic insufficiency, and for diabetes and dysglycaemia, there were 4 and 2 patients respectively (31.3% altogether). In conclusion, ABCC8/KCNJ11 mutation is a common mutation among the persistent CHI in our cohort. A low threshold for genetic testing can be considered among the persistent CHI patients who were macrosomic as ABCC8/KCNJ11 mutation need to be suspected. Furthermore, the genetic result is helpful to plan for the management of the patients with ABCC8/KCNJ11 mutation.