Localized Islet Nuclear Enlargement Hyperinsulinism (LINE-HI) Due to ABCC8 and GCK Mosaic Mutations

Overview

Journal Eur J Endocrinol

Publisher Oxford University Press

Specialty Endocrinology

Date 2022 Jun 8

PMID 35674212

Authors

Kara E Boodhansingh

Zhongying Yang

Changhong Li

Pan Chen

Katherine Lord

Susan A Becker

Lisa J States

N Scott Adzick

Tricia Bhatti

Show-Ling Shyng

Arupa Ganguly

Charles A Stanley

Diva D De Leon

Affiliations

Soon will be listed here.

Abstract

Objective: Congenital hyperinsulinism (HI) is the most common cause of persistent hypoglycemia in children. In addition to typical focal or diffuse HI, some cases with diazoxide-unresponsive congenital HI have atypical pancreatic histology termed Localized Islet Nuclear Enlargement (LINE) or mosaic HI, characterized by histologic features similar to diffuse HI, but confined to only a region of pancreas. Our objective was to characterize the phenotype and genotype of children with LINE-HI.

Design: The phenotype and genotype features of 12 children with pancreatic histology consistent with LINE-HI were examined.

Methods: We compiled clinical features of 12 children with LINE-HI and performed next-generation sequencing on specimens of pancreas from eight of these children to look for mosaic mutations in genes known to be associated with diazoxide-unresponsive HI (ABCC8, KCNJ11, and GCK).

Results: Children with LINE-HI had lower birth weights and later ages of presentation compared to children with typical focal or diffuse HI. Partial pancreatectomy in LINE-HI cases resulted in euglycemia in 75% of cases; no cases have developed diabetes. Low-level mosaic mutations were identified in the pancreas of six cases with LINE-HI (three in ABCC8, three in GCK). Expression studies confirmed that all novel mutations were pathogenic.

Conclusion: These results indicate that post-zygotic low-level mosaic mutations of known HI genes are responsible for some cases of LINE-HI that lack an identifiable germ-line mutation and that partial pancreatectomy may be curative for these cases.

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