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. 2022 Jan 5;59(2):105–109. doi: 10.1007/s13312-022-2438-0

Molecular Characterization and Management of Congenital Hyperinsulinism: A Tertiary Centre Experience

Rajni Sharma 1, Kakali Roy 1, Amit Kumar Satapathy 2, Anil Kumar 1, Pamali Mahasweta Nanda 1, Nishikant Damle 3, Jayne A L Houghton 4, Sarah E Flanagan 5, Venkatesan Radha 6, Viswanathan Mohan 6, Vandana Jain 1,✉
PMCID: PMC8913199  PMID: 34992182

Abstract

Background

There is limited data from India regarding medical management of congenital hyperinsulinism (CHI).

Objective

To study the molecular diagnosis, medical management and outcomes of children with CHI.

Study design

Ambispective.

Participants

Children with CHI admitted in from December, 2011 till March, 2020 at a tertiary care referral hospital.

Outcomes

Clinical and genetic profile, treatment, and response

Results

42 children with a median age of 3 days (range 1 day to 6 years) were enrolled, of which 23 (54.7%) were diazoxide-responsive. Mutations were identified in 28 out of 41 (68.2%) patients. The commonest gene affected was ABCC8 in 22 patients. The pathogenic variant c.331G>A in ABCC8 gene was identified in 6 unrelated cases from one community. Good response to daily octreotide was seen in 13 of the 19 (68.4%) diazoxide-unresponsive patients. Monthly long-acting octreotide was initiated and daily octreotide could be stopped or tapered in 9 patients. Sirolimus was tried with variable response in 6 patients but was discontinued in 5 due to adverse effects. Four patients had focal CHI, of which one underwent partial pancreatic resection. The disease severity reduced with age and neurodevelopment was good in the patients with identifiable genetic defects who were optimally managed.

Conclusions

Medical management of CHI is effective, if compliance can be ensured, with good quality of life and neurological outcomes.

Electronic Supplementary Material

Supplementary material is available for this article at 10.1007/s13312-022-2438-0 and is accessible for authorized users.

Keywords: ABCC8 gene, Diazoxide, Hypoglycemia, Octreotide, Sirolimus

Electronic supplementary material

13312_2022_2438_MOESM1_ESM.pdf (177.9KB, pdf)

Web Table I: Summary of Genetic Mutations, Treatment and Follow-Up in Patients with Congenital Hyperinsulinism (N=40)

Contributors: RS, KR: prepared the manuscript; RS, KR, AS, PMN, AK, ND, VJ: involved the diagnostic work up, clinical management of patients and data collection; SEF, JALH, VR, VM: performed the genetic studies; VJ: conceived the study, initiated the collaborations for genetic testing, critically reviewed the manuscript. All authors approved the final manuscript and are accountable for all aspects of the work.

Funding: SEF has a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant Number 105636/Z/14/Z). Costs associated with the genetic testing performed in Exeter were covered by funds donated by Congenital Hyper-insulinism International (a 501(c)3 organization). Costs of genetic testing at MDRF Chennai were covered by Indian Council for Medical Research (ICMR), New Delhi, India, through a project awarded to VR (no. 57/2/2014-NCD-II).

Ethics clearance: Ethics committee of AIIMS, New Delhi; No. IEC 109/5.2.21, RP-26/2021, dated February 05, 2021.

Competing interests: None stated.

Footnotes

Note: Additional material related to this study is available with the online version at https://www.indianpediatrics.net

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

13312_2022_2438_MOESM1_ESM.pdf (177.9KB, pdf)

Web Table I: Summary of Genetic Mutations, Treatment and Follow-Up in Patients with Congenital Hyperinsulinism (N=40)

Articles from Indian Pediatrics are provided here courtesy of Nature Publishing Group

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