Genetics and natural history of non-pancreatectomised patients with congenital hyperinsulinism due to variants in ABCC8.

Patients with congenital hyperinsulinism due to ABCC8 variants generally present severe hypoglycaemia and those who do not respond to medical treatment typically undergo pancreatectomy. Few data exist on the natural history of non-pancreatectomised patients.This work aims to describe the genetic characteristics and natural history in a cohort of non-pancreatectomised patients with congenital hyperinsulinism due to variants in the ABCC8 gene.Ambispective study of patients with congenital hyperinsulinism with pathogenic or likely pathogenic variants in ABCC8 treated in the last 48 years and who were non-pancreatectomised. Continuous Glucose Monitoring (CGM) has been periodically performed in all patients since 2003. An oral glucose tolerance test (OGTT) was performed if hyperglycemia was detected in the CGM.Eighteen non-pancreatectomised patients with ABCC8 variants were included. Seven (38.9%) patients were heterozygous, eight (44.4%) compound heterozygous, two (11.1%) homozygous, and one patient carried two variants with incomplete familial segregation studies. Seventeen patients were followed-up and twelve (70.6%) of them evolved to spontaneous resolution (median age 6.0±4years; range:1-14). Five out of these twelve patients (41.7%) subsequently progressed to diabetes with insufficient insulin secretion. Evolution to diabetes was more frequent in patients with biallelic variants in the ABCC8 gene.The high remission rate observed in our cohort makes conservative medical treatment a reliable strategy for the management of patients with congenital hyperinsulinism due to ABCC8 variants. In addition, a periodic follow-up of glucose metabolism after remission is recommended as a significant proportion of patients evolved to impaired glucose tolerance or diabetes (biphasic phenotype).© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Citation

María Clemente, Patricia Cobo, María Antolín, Ariadna Campos, Diego Yeste, Rosangela Tomasini, María Caimarí, Miriam Masas, Elena García-Arumí, Mónica Fernandez-Cancio, Noelia Baz-Redón, Núria Camats-Tarruella. Genetics and natural history of non-pancreatectomised patients with congenital hyperinsulinism due to variants in ABCC8. The Journal of clinical endocrinology and metabolism. 2023 May 22

PMID: 37216904

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