Congenital hyperinsulinism and glycogenosis-like phenotype due to a novel HNF4A mutation

Staník, Juraj; Škopková, Martina; Brennerova, Katarina; Daniš, Daniel; Rosolankova, Monika; Šalingová, Anna; Bzdúch, Vladimír; Klimeš, I; Gašperíková, Daniela

doi:10.1016/j.diabres.2017.02.014

Cited by 14 publications

(9 citation statements)

References 22 publications

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“…This type of CHI due to HNF1A/HNF4A gene mutations is characterized with macrosomia and a clinical severity varying form mild transient hypoglycaemia to severe HH responsive to diazoxide therapy (25, 143, 147–149). In addition, a glycogenosis-like phenotype, characterized with glycogen accumulation in red blood cells, elevated liver enzymes and increased hepatic echogenicity on ultrasound examination, has been reported in CHI due to HNF4A gene mutations (150, 151). Although CHI due to HNF1A and HNF4A mutations is rare, in some series of diazoxide-responsive HH, these mutations have been shown as one of the most common genetic etiology (149, 152).…”

Section: Chi Due To Defects In Transcription Factorsmentioning

confidence: 99%

The Genetic and Molecular Mechanisms of Congenital Hyperinsulinism

et al. 2019

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Congenital hyperinsulinism (CHI) is a heterogenous and complex disorder in which the unregulated insulin secretion from pancreatic beta-cells leads to hyperinsulinaemic hypoglycaemia. The severity of hypoglycaemia varies depending on the underlying molecular mechanism and genetic defects. The genetic and molecular causes of CHI include defects in pivotal pathways regulating the secretion of insulin from the beta-cell. Broadly these genetic defects leading to unregulated insulin secretion can be grouped into four main categories. The first group consists of defects in the pancreatic K ATP channel genes ( ABCC8 and KCNJ11 ). The second and third categories of conditions are enzymatic defects (such as GDH, GCK, HADH) and defects in transcription factors (for example HNF1α, HNF4α) leading to changes in nutrient flux into metabolic pathways which converge on insulin secretion. Lastly, a large number of genetic syndromes are now linked to hyperinsulinaemic hypoglycaemia. As the molecular and genetic basis of CHI has expanded over the last few years, this review aims to provide an up-to-date knowledge on the genetic causes of CHI.

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Section: Chi Due To Defects In Transcription Factorsmentioning

confidence: 99%

The Genetic and Molecular Mechanisms of Congenital Hyperinsulinism

et al. 2019

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“…CHI due to mutations in both HNF1A and HNF4A are characterized by macrosomic birth and mild transient to severe diazoxide-responsive HH ( 6 , 13 , 52 , 79 , 83 , 84 , 85 ). CHI due to HNF4A gene has been reported with increased levels of glycogen in erythrocytes, elevated liver transaminases and increased echogenicity on liver ultrasonography, suggesting a glycogenosis-like phenotype ( 86 , 87 ). In some patients with diazoxide responsive HH, mutations in HNF1A and HNF4A may be common ( 85 , 88 ).…”

Section: Introductionmentioning

confidence: 99%

Congenital Hyperinsulinism: Diagnosis and Treatment Update

Demirbilek¹,

Hussain²

2018

Jcrpe

105

112

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Pancreatic β-cells are finely tuned to secrete insulin so that plasma glucose levels are maintained within a narrow physiological range (3.5-5.5 mmol/L). Hyperinsulinaemic hypoglycaemia (HH) is the inappropriate secretion of insulin in the presence of low plasma glucose levels and leads to severe and persistent hypoglycaemia in neonates and children. Mutations in 12 different key genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, UCP2, HNF4A, HNF1A, HK1, PGM1 and PMM2) that are involved in the regulation of insulin secretion from pancreatic β-cells have been described to be responsible for the underlying molecular mechanisms leading to congenital HH. In HH due to the inhibitory effect of insulin on lipolysis and ketogenesis there is suppressed ketone body formation in the presence of hypoglycaemia thus leading to increased risk of hypoglycaemic brain injury. Therefore, a prompt diagnosis and immediate management of HH is essential to avoid hypoglycaemic brain injury and long-term neurological complications in children. Advances in molecular genetics, imaging techniques (18F-DOPA positron emission tomography/computed tomography scanning), medical therapy and surgical advances (laparoscopic and open pancreatectomy) have changed the management and improved the outcome of patients with HH. This review article provides an overview to the background, clinical presentation, diagnosis, molecular genetics and therapy in children with different forms of HH.

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“…CHI due to mutations in both HNF1A and HNF4A are characterized by macrosomic birth and mild transient to severe diazoxide-responsive HH (6,13,52,79,83,84,85). CHI due to HNF4A gene has been reported with increased levels of glycogen in erythrocytes, elevated liver transaminases and increased echogenicity on liver ultrasonography, suggesting a glycogenosislike phenotype (86,87). In some patients with diazoxide responsive HH, mutations in HNF1A and HNF4A may be common (85,88).…”

Section: F) Hepatocyte Nuclear Factor (Hnf) 1aand4a (Hnf1aand4a) and Chimentioning

confidence: 99%