Dataset Information

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

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.

Setting

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.

SUBMITTER: Sharma R

PROVIDER: S-EPMC8913199 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Publications

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

Sharma Rajni R Roy Kakali K Satapathy Amit Kumar AK Kumar Anil A Nanda Pamali Mahasweta PM Damle Nishikant N Houghton Jayne A L JAL Flanagan Sarah E SE Radha Venkatesan V Mohan Viswanathan V Jain Vandana V

Indian pediatrics 20220105 2

<h4>Background</h4>There is limited data from India regarding medical management of congenital hyperinsulinism (CHI).<h4>Objective</h4>To study the molecular diagnosis, medical management and outcomes of children with CHI.<h4>Study design</h4>Ambispective.<h4>Setting</h4><h4>Participants</h4>Children with CHI admitted in from December, 2011 till March, 2020 at a tertiary care referral hospital.<h4>Outcomes</h4>Clinical and genetic profile, treatment, and response.<h4>Results</h4>42 children with ...[more]

PMID: 34992182

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Project description:The importance of glucokinase (GK) in the regulation of insulin secretion has been highlighted by the phenotypes of individuals with activating and inactivating mutations in the glucokinase gene (GCK). Here we report 10 individuals with congenital hyperinsulinism (HI) caused by eight unique activating mutations of GCK. Six are novel and located near previously identified activating mutations sites. The first recognized episode of hypoglycemia in these patients occurred between birth and 24 years, and the severity of the phenotype was also variable. Mutant enzymes were expressed and purified for enzyme kinetics in vitro. Mutant enzymes had low glucose half-saturation concentration values and an increased enzyme activity index compared with wild-type GK. We performed functional evaluation of islets from the pancreata of three children with GCK-HI who required pancreatectomy. Basal insulin secretion in perifused GCK-HI islets was normal, and the response to glyburide was preserved. However, the threshold for glucose-stimulated insulin secretion in perifused glucokinase hyperinsulinism (GCK-HI) islets was decreased, and glucagon secretion was greatly suppressed. Our evaluation of novel GCK disease-associated mutations revealed that the detrimental effects of these mutations on glucose homeostasis can be attributed not only to a lowering of the glucose threshold of insulin secretion but also to a decreased counterregulatory glucagon secretory response.Article highlightsOur evaluation of six novel and two previously published activating GCK mutations revealed that the detrimental effects of these mutations on glucose homeostasis can be attributed not only to a lowering of the glucose threshold of insulin secretion but also to a decreased counterregulatory glucagon secretory response. These studies provide insights into the pathophysiology of GCK-hyperinsulinism and the dual role of glucokinase in β-cells and α-cells to regulate glucose homeostasis.

Dataset Information

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

Background

Objective

Study design

Setting

Participants

Outcomes

Results

Conclusions

Publications

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

Similar Datasets

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