Prenatal Diagnosis and Postnatal Management of Diffuse Congenital Hyperinsulinism: A Case Report

Peranteau, William H.; Ganguly, Arupa; Steinmuller, L.; Thornton, Paul; Johnson, MP; Howell, Lori J.; Stanley, Charles A.; Adzick, N. Scott

doi:10.1159/000095664

Cited by 8 publications

(4 citation statements)

References 43 publications

(33 reference statements)

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“…This was particularly the case in a patient with compound heterozygous R74W/R1215Q mutations who had a greater than normal insulin response to tolbutamide. Overall, the in vitro functional analysis provides valuable information by allowing prediction of phenotype based on genotype to facilitate disease diagnosis and management (40). Therapeutic implications.…”

Section: Discussionmentioning

confidence: 99%

Congenital Hyperinsulinism–Associated ABCC8 Mutations That Cause Defective Trafficking of ATP-Sensitive K+ Channels

et al. 2007

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Congenital hyperinsulinism (CHI) is a disease characterized by persistent insulin secretion despite severe hypoglycemia. Mutations in the pancreatic ATP-sensitive K ؉ (K ATP ) channel proteins sulfonylurea receptor 1 (SUR1) and Kir6.2, encoded by ABCC8 and KCNJ11, respectively, is the most common cause of the disease. Many mutations in SUR1 render the channel unable to traffic to the cell surface, thereby reducing channel function. Previous studies have shown that for some SUR1 trafficking mutants, the defects could be corrected by treating cells with sulfonylureas or diazoxide. The purpose of this study is to identify additional mutations that cause channel biogenesis/trafficking defects and those that are amenable to rescue by pharmacological chaperones. Fifteen previously uncharacterized CHI-associated missense SUR1 mutations were examined for their biogenesis/trafficking defects and responses to pharmacological chaperones, using a combination of immunological and functional assays. Twelve of the 15 mutations analyzed cause reduction in cell surface expression of K ATP channels by >50%. Sulfonylureas rescued a subset of the trafficking mutants. By contrast, diazoxide failed to rescue any of the mutants. Strikingly, the mutations rescued by sulfonylureas are all located in the first transmembrane domain of SUR1, designated as TMD0. All TMD0 mutants rescued to the cell surface by the sulfonylurea tolbutamide could be subsequently activated by metabolic inhibition on tolbutamide removal. Our study identifies a group of CHI-causing SUR1 mutations for which the resulting K ATP channel trafficking and expression defects may be corrected pharmacologically to restore channel function. Diabetes

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Section: Discussionmentioning

confidence: 99%

Congenital Hyperinsulinism–Associated ABCC8 Mutations That Cause Defective Trafficking of ATP-Sensitive K+ Channels

et al. 2007

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“…Patients with known or suspected genetic defect of the SUR and Kir 6.2 subunits may not fully respond to diazoxide therapy. 35 These alterations have been demonstrated in families with hyperinsulinism who respond poorly to diazoxide therapy. 36 Diazoxide has historically been a first line agent, however patients experiencing hypoglycemia during the neonatal period are less responsive than those presenting in infancy.…”

Section: Diazoxidementioning

confidence: 99%

Management Strategies for Neonatal Hypoglycemia

Sweet

Grayson

Polak

2013

The Journal of Pediatric Pharmacology and Therapeutics

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While hypoglycemia occurs commonly among neonates, treatment can be challenging if hypoglycemia persists beyond the first few days of life. This review discusses the available treatment options for both transient and persistent neonatal hypoglycemia. These treatment options include dextrose infusions, glucagon, glucocorticoids, diazoxide, octreotide, and nifedipine. A stepwise, practical approach to the management of these patients is offered.

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“…In order to take the correct surgical approach a new technique, involving 18 Fluoro-L-Dopa position emission tomography (PET) scanning, has been developed to distinguish between focal and diffuse forms of CHI [54][55][56]. Prenatal diagnosis of CHI is now also available for KCNJ11 and ABCC8 mutations, which allows for immediate medical management of CHI at the time of birth [57]. This is also extremely useful for parents who have already had one affected child.…”

Section: Treatment Of Congenital Hyperinsulinismmentioning

confidence: 99%

Pancreatic β-cell KATP channels: Hypoglycaemia and hyperglycaemia

Bennett

James

Hussain

2010

Rev Endocr Metab Disord

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The pancreatic β-cell ATP-sensitive K(+) channel (K(ATP) channel) plays a critical role in glucose homeostasis by linking glucose metabolism to electrical excitability and insulin secretion. Changes in the intracellular ratio of ATP/ADP mediate the metabolic regulation of channel activity. The β-cell K(ATP) channel is a hetero-octameric complex composed of two types of subunits: four inward-rectifying potassium channel pore-forming (Kir6.2) subunits and four high-affinity sulfonylurea receptor 1 (SUR1) subunits. Kir6.2 and SUR1 are encoded by the genes KCNJ11 and ABCC8, respectively. Mutations in these genes can result in congenital hyperinsulinism and permanent neonatal diabetes. This review highlights the important role of the β-cell K(ATP) channel in glucose physiology and provides an introduction to some of the other review articles in this special edition of the Reviews in Endocrine and Metabolic Disorders.

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Prenatal Diagnosis and Postnatal Management of Diffuse Congenital Hyperinsulinism: A Case Report

Cited by 8 publications

References 43 publications

Congenital Hyperinsulinism–Associated ABCC8 Mutations That Cause Defective Trafficking of ATP-Sensitive K+ Channels

Congenital Hyperinsulinism–Associated ABCC8 Mutations That Cause Defective Trafficking of ATP-Sensitive K+ Channels

Management Strategies for Neonatal Hypoglycemia

Pancreatic β-cell KATP channels: Hypoglycaemia and hyperglycaemia

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