The evolving course of <i><scp>HNF</scp>4A</i> hyperinsulinaemic hypoglycaemia—a case series

McGlacken-Byrne, SM; Hawkes, Colin P.; Flanagan, Sarah E.; Ellard, Sian; McDonnell, Ciara M.; Murphy, Nuala

doi:10.1111/dme.12259

Cited by 21 publications

(14 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The pathogenesis of other mutations, such as those reported in UCP2, is still debated and needs further clarification [22]. In those with CHI attributable to HNF4A mutations, hypoglycaemia switches to hyperglycaemia and maturity-onset diabetes at a variable age [24]. In those with CHI attributable to HNF4A mutations, hypoglycaemia switches to hyperglycaemia and maturity-onset diabetes at a variable age [24].…”

Section: Genetic Forms Of Congenital Hyperinsulinismmentioning

confidence: 99%

“…Genetic forms of CHI do not have consistent disease trajectories; while homozygous and compound heterozygous mutations are likely to suggest permanent forms of CHI, recent experience suggests reduction in the severity of hyperinsulinism over time, even in those with severe forms of disease [23]. In those with CHI attributable to HNF4A mutations, hypoglycaemia switches to hyperglycaemia and maturity-onset diabetes at a variable age [24]. In those with activating GCK mutations causing CHI, some require no treatment, while others are responsive to diazoxide and yet others are severe enough to require pancreatectomy [25].…”

Section: What's New?mentioning

confidence: 99%

“…Diabetes has been well recognized in dominant genetic forms of CHI, such as with HNF4A and some ABCC8 variants [14,15,24]. For the majority of ABCC8 dominant pathogenic variants, there is no evidence of predictability; however, in the absence of evidence of natural history for these variants, it may be wise to counsel families to be vigilant for symptoms of diabetes in later life.…”

Section: Diabetesmentioning

confidence: 99%

See 2 more Smart Citations

Therapies and outcomes of congenital hyperinsulinism‐induced hypoglycaemia

et al. 2018

View full text Add to dashboard Cite

Congenital hyperinsulinism is a rare disease, but is the most frequent cause of persistent and severe hypoglycaemia in early childhood. Hypoglycaemia caused by excessive and dysregulated insulin secretion (hyperinsulinism) from disordered pancreatic β cells can often lead to irreversible brain damage with lifelong neurodisability. Although congenital hyperinsulinism has a genetic cause in a significant proportion (40%) of children, often being the result of mutations in the genes encoding the KATP channel (ABCC8 and KCNJ11), not all children have severe and persistent forms of the disease. In approximately half of those without a genetic mutation, hyperinsulinism may resolve, although timescales are unpredictable. From a histopathology perspective, congenital hyperinsulinism is broadly grouped into diffuse and focal forms, with surgical lesionectomy being the preferred choice of treatment in the latter. In contrast, in diffuse congenital hyperinsulinism, medical treatment is the best option if conservative management is safe and effective. In such cases, children receiving treatment with drugs, such as diazoxide and octreotide, should be monitored for side effects and for signs of reduction in disease severity. If hypoglycaemia is not safely managed by medical therapy, subtotal pancreatectomy may be required; however, persistent hypoglycaemia may continue after surgery and diabetes is an inevitable consequence in later life. It is important to recognize the negative cognitive impact of early‐life hypoglycaemia which affects half of all children with congenital hyperinsulinism. Treatment options should be individualized to the child/young person with congenital hyperinsulinism, with full discussion regarding efficacy, side effects, outcomes and later life impact.

show abstract

Section: Genetic Forms Of Congenital Hyperinsulinismmentioning

confidence: 99%

Section: What's New?mentioning

confidence: 99%

Section: Diabetesmentioning

confidence: 99%

See 1 more Smart Citation

Therapies and outcomes of congenital hyperinsulinism‐induced hypoglycaemia

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Infants born to a parent with HNF4A MODY require glucose monitoring after delivery as at least 10% of affected neonates have hypoglycaemia (blood glucose <2.5 mmol/l) [34,40]. Severe hyperinsulinaemic hypoglycaemia (blood glucose 0.8-2.5mmol/l for >24 h) may require prolonged treatment (intravenous glucose infusion, glucagon and diazoxide/ chlorthiazide) as the hypoglycaemia can persist for months or years [37,40,41]. The increased birth weight and neonatal hypoglycaemia are a result of hyperinsulinism before and after birth [34].…”

Section: Reports On Pregnancymentioning

confidence: 99%

Management of sulfonylurea‐treated monogenic diabetes in pregnancy: implications of placental glibenclamide transfer

et al. 2017

View full text Add to dashboard Cite

The optimum treatment for HNF1A/HNF4A maturity‐onset diabetes of the young and ATP‐sensitive potassium (KATP) channel neonatal diabetes, outside pregnancy, is sulfonylureas, but there is little evidence regarding the most appropriate treatment during pregnancy. Glibenclamide has been widely used in the treatment of gestational diabetes, but recent data have established that glibenclamide crosses the placenta and increases risk of macrosomia and neonatal hypoglycaemia. This raises questions about its use in pregnancy. We review the available evidence and make recommendations for the management of monogenic diabetes in pregnancy. Due to the risk of stimulating increased insulin secretion in utero, we recommend that in women with HNF1A/ HNF4A maturity‐onset diabetes of the young, those with good glycaemic control who are on a sulfonylurea per conception either transfer to insulin before conception (at the risk of a short‐term deterioration of glycaemic control) or continue with sulfonylurea (glibenclamide) treatment in the first trimester and transfer to insulin in the second trimester. Early delivery is needed if the fetus inherits an HNF4A mutation from either parent because increased insulin secretion results in ~800‐g weight gain in utero, and prolonged severe neonatal hypoglycaemia can occur post‐delivery. If the fetus inherits a KATP neonatal diabetes mutation from their mother they have greatly reduced insulin secretion in utero that reduces fetal growth by ~900 g. Treating the mother with glibenclamide in the third trimester treats the affected fetus in utero, normalising fetal growth, but is not desirable, especially in the high doses used in this condition, if the fetus is unaffected. Prospective studies of pregnancy in monogenic diabetes are needed.

show abstract

“…My editor's choice is from McGlacken‐Byrne and colleagues , who present a case series of three infants diagnosed with mutations in HNF4A, two of which were de novo (not present in the parents). All infants were macrosomic and presented with hyperinsulinaemic hypoglycaemia soon after birth; all three required continuing treatment with diazoxide.…”

mentioning

confidence: 99%

The variable faces of monogenic diabetes

Hitman

2013

Diabet. Med.

View full text Add to dashboard Cite

The variable faces of monogenic diabetes Diabet. Med. 31, 1 (2014) With advances in genomic research, it is now possible in some people with diabetes to make a precise molecular diagnosis that will help inform clinical care of the individual and any other affected family members. Autosomal dominant monogenic diabetes (also known as maturity-onset diabetes of the young; MODY) was first highlighted by Cammidge in 1928 [1] when he stated:

show abstract

The evolving course of HNF4A hyperinsulinaemic hypoglycaemia—a case series

Cited by 21 publications

References 20 publications

Therapies and outcomes of congenital hyperinsulinism‐induced hypoglycaemia

Therapies and outcomes of congenital hyperinsulinism‐induced hypoglycaemia

Management of sulfonylurea‐treated monogenic diabetes in pregnancy: implications of placental glibenclamide transfer

The variable faces of monogenic diabetes

Contact Info

Product

Resources

About