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Diazoxide is the first-line treatment for patients with hyperinsulinaemic hypoglycaemia (HH). Approximately 50% of patients with HH are diazoxide resistant. However, marked diazoxide sensitivity resulting in severe hyperglycaemia is extremely uncommon and not reported previously in the context of HH due to HNF4A mutation. We report a novel observation of exceptional diazoxide sensitivity in a patient with HH due to HNF4A mutation. A female infant presented with severe persistent neonatal hypoglycaemia and was diagnosed with HH. Standard doses of diazoxide (5 mg/kg/day) resulted in marked hyperglycaemia (maximum blood glucose 21.6 mmol/L) necessitating discontinuation of diazoxide. Lower dose of diazoxide (1.5 mg/kg/day) successfully controlled HH in the proband, which was subsequently confirmed to be due to a novel HNF4A mutation. At 3 years of age, the patient maintains age appropriate fasting tolerance on low dose diazoxide (1.8 mg/kg/day) and has normal development. Diagnosis in proband's mother and maternal aunt, both of whom carried HNF4A mutation and had been diagnosed with presumed type 1 and type 2 diabetes mellitus, respectively, was revised to maturity-onset diabetes of young (MODY). Proband's 5-year-old maternal cousin, also carrier of HNF4A mutation, had transient neonatal hypoglycaemia. To conclude, patients with HH due to HNF4A mutation may require lower diazoxide than other group of patients with HH. Educating the families about the risk of marked hyperglycaemia with diazoxide is essential. The clinical phenotype of HNF4A mutation can be extremely variable. Learning points: Awareness of risk of severe hyperglycaemia with diazoxide is important and patients/families should be accordingly educated. Some patients with HH due to HNF4A mutations may require lower than standard doses of diazoxide. The clinical phenotype of HNF4A mutation can be extremely variable.
This article was published in the following journal.
Name: Endocrinology, diabetes & metabolism case reports
We report a case of partial diazoxide responsiveness in a child with severe congenital hyperinsulinaemic hypoglycaemia (CHI) due to a homozygous ABCC8 mutation. A term baby, with birth weight 3.8 kg, ...
Background Congenital hyperinsulinism (CHI) occurs due to an unregulated insulin secretion from the pancreatic β-cells resulting in hypoglycaemia. Causative mutations in multiple genes have been repo...
Initially described as an uncommon presenting feature of Sotos syndrome (SoS), over the last decades, congenital hyperinsulinaemic hypoglycaemia (CHI) has been increasingly reported in association wit...
The study aimed to screen the HNF1A and HNF4A mutation in a large Chinese cohort of high clinical suspicion of maturity-onset diabetes of the young (MODY) patients and characterize the clinical featur...
This experimental study is planned to investigate the impact of hypoglycaemia on platelet activation parameters (PAP) during a hyperinsulinaemic hypoglycaemic clamp study. The hypothesis t...
Postprandial hyperinsulinaemic hypoglycaemia is an increasingly recognized adverse side effect of bariatric surgery. Affected individuals experience low glucose levels 1-3 hours after inta...
The purpose of this study is to determine whether there is an additive effect of metformine on the weight reduction of obese hyperinsulinemic men who are treated with diazoxide.
Diazoxide is an oral hyperglycemic medication. Diazoxide has been proven effective for treating hypoglycemia in infants and children with some types of persistent hyperinsulinemic hypogly...
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A benzothiadiazine derivative that is a peripheral vasodilator used for hypertensive emergencies. It lacks diuretic effect, apparently because it lacks a sulfonamide group.
Mutation process that restores the wild-type PHENOTYPE in an organism possessing a mutationally altered GENOTYPE. The second "suppressor" mutation may be on a different gene, on the same gene but located at a distance from the site of the primary mutation, or in extrachromosomal genes (EXTRACHROMOSOMAL INHERITANCE).
A type of mutation in which a number of NUCLEOTIDES deleted from or inserted into a protein coding sequence is not divisible by three, thereby causing an alteration in the READING FRAMES of the entire coding sequence downstream of the mutation. These mutations may be induced by certain types of MUTAGENS or may occur spontaneously.
Concept which describes the incremental effects of MUTATION in living organisms.
A mutation that causes a decrease in or elimination of a gene product's activity.
Pediatrics is the general medicine of childhood. Because of the developmental processes (psychological and physical) of childhood, the involvement of parents, and the social management of conditions at home and at school, pediatrics is a specialty. With ...