Stem Cell Based Models in Congenital Hyperinsulinism – Perspective on Practicalities and Possibilities

Lithovius, Väinö; Otonkoski, Timo

doi:10.3389/fendo.2022.837450

Cited by 4 publications

(2 citation statements)

References 76 publications

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“…Thus, there is still a great need to find more effective anti-hypoglycaemic medications for patients with severe CHI, and several research projects are ongoing ( 23 , 24 ). Pluripotent stem cell-derived islets might help develop more efficient medications, thus avoiding a near-total pancreatectomy ( 25 ).…”

Section: Discussionmentioning

confidence: 99%

Case report: Exceptional transmission of congenital hyperinsulinism from a focal CHI mother to her diffuse CHI dichorionic diamniotic twins

Telehuz,

Plesa,

Bouilloud

et al. 2024

Front. Endocrinol.

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We present the case of a 36-year-old female who was diagnosed at birth with CHI that caused severe hypoglycaemia unresponsive to Diazoxide. Subtotal pancreatectomy was performed at the age of three weeks. Later, histological analysis of her pancreas in a research setting revealed a focal form of CHI. Genetic testing was not available at that time. The patient developed pancreatic exocrine deficiency and insulin-dependent diabetes at the age of 9 years. In 2016, a genetic test revealed a missense heterozygous variant in the ABCC8 gene inherited from her father and classified as having a recessive inheritance. The geneticist concluded that the risk of CHI for her offspring would be low (1/600), making pregnancy favourable. As there was no consanguinity in the family, testing the future father was deemed unnecessary (carrier frequency 1/150 in the general population). The pregnancy occurred spontaneously in 2020 and at a gestational age of 28 weeks, the mother went into premature labour. An emergency C-section was performed in April 2021 resulting in the birth of bichorial bi-amniotic male twins. Following birth, both newborns experienced persistent severe hypoglycaemia which required glucagon treatment and intravenous glucose infusion initially, followed by Diazoxide from day 51 after birth, without satisfactory response. Continuous intravenous Octreotide treatment was introduced on day 72. Due to the recurrence of hypoglycaemia episodes despite reaching maximum doses of Octreotide, from day 92 the treatment was switched to Pasireotide. Genetic tests revealed the same genotypes for both infants: the exon 39 missense variant (c.4716C>A; p.Ser1572Arg) inherited from their mother and a truncating variant in exon 28 (c.3550del; p.Val1184*), inherited from their asymptomatic father. As a result of inheriting two recessive variants of the ABCC8 gene, the children were diagnosed with a diffuse form of CHI, consistent with the diazoxide-unresponsive presentation. This situation is very rare outside consanguinity. This case emphasises the significance of genetic counselling for individuals with a history of rare diseases outside the context of consanguinity, as there is a potential risk of recurrence. Prenatal diagnosis can lead to better outcomes for affected neonates, as well as help families make informed decisions about future pregnancies.

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Section: Discussionmentioning

confidence: 99%

Case report: Exceptional transmission of congenital hyperinsulinism from a focal CHI mother to her diffuse CHI dichorionic diamniotic twins

Telehuz,

Plesa,

Bouilloud

et al. 2024

Front. Endocrinol.

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“…Finally, there is currently no animal models to test the in vivo feasibility of pharmacological chaperone therapy. Recent development of induced pluripotent stem cells (iPSCs) derived from a CHI patient carrying a homozygous trafficking mutation SUR1-V187D ( 107 ) could serve as an intermediate experimental model to test the effect of reversible K ATP pharmacological chaperones such as tolbutamide.…”

Section: Treatment Of K Atp -Hi: Challenges and Op...mentioning

confidence: 99%

KATP channel mutations in congenital hyperinsulinism: Progress and challenges towards mechanism-based therapies

ElSheikh

Show-Ling

2023

Front. Endocrinol.

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Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycemia in infancy/childhood and is a serious condition associated with severe recurrent attacks of hypoglycemia due to dysregulated insulin secretion. Timely diagnosis and effective treatment are crucial to prevent severe hypoglycemia that may lead to life-long neurological complications. In pancreatic β-cells, adenosine triphosphate (ATP)-sensitive K+ (KATP) channels are a central regulator of insulin secretion vital for glucose homeostasis. Genetic defects that lead to loss of expression or function of KATP channels are the most common cause of HI (KATP-HI). Much progress has been made in our understanding of the molecular genetics and pathophysiology of KATP-HI in the past decades; however, treatment remains challenging, in particular for patients with diffuse disease who do not respond to the KATP channel activator diazoxide. In this review, we discuss current approaches and limitations on the diagnosis and treatment of KATP-HI, and offer perspectives on alternative therapeutic strategies.

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Stem cells in neonatal diseases: An overview

Chaubey

Bhandari

2022

Seminars in Fetal and Neonatal Medicine

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Stem Cell Based Models in Congenital Hyperinsulinism – Perspective on Practicalities and Possibilities

Cited by 4 publications

References 76 publications

Case report: Exceptional transmission of congenital hyperinsulinism from a focal CHI mother to her diffuse CHI dichorionic diamniotic twins

Case report: Exceptional transmission of congenital hyperinsulinism from a focal CHI mother to her diffuse CHI dichorionic diamniotic twins

KATP channel mutations in congenital hyperinsulinism: Progress and challenges towards mechanism-based therapies

Stem cells in neonatal diseases: An overview

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