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Exceptional diazoxide sensitivity in hyperinsulinaemic hypoglycaemia due to a novel HNF4A mutation.

Abstract

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.

Authors+Show Affiliations

Department of Paediatric Endocrinology, Variety Club Children's Hospital, King's College Hospital NHS Foundation Trust, London, UK.Department of Paediatric Endocrinology, Variety Club Children's Hospital, King's College Hospital NHS Foundation Trust, London, UK.Department of Neonatology, King's College Hospital NHS Foundation Trust, London, UK.Institute of Biomedical and Clinical Science, University of Exeter, Exeter, UK.Department of Paediatric Endocrinology, Variety Club Children's Hospital, King's College Hospital NHS Foundation Trust, London, UK.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31096182

Citation

Arya, Ved Bhushan, et al. "Exceptional Diazoxide Sensitivity in Hyperinsulinaemic Hypoglycaemia Due to a Novel HNF4A Mutation." Endocrinology, Diabetes & Metabolism Case Reports, vol. 2019, 2019.
Arya VB, Kalitsi J, Hickey A, et al. Exceptional diazoxide sensitivity in hyperinsulinaemic hypoglycaemia due to a novel HNF4A mutation. Endocrinol Diabetes Metab Case Rep. 2019;2019.
Arya, V. B., Kalitsi, J., Hickey, A., Flanagan, S. E., & Kapoor, R. R. (2019). Exceptional diazoxide sensitivity in hyperinsulinaemic hypoglycaemia due to a novel HNF4A mutation. Endocrinology, Diabetes & Metabolism Case Reports, 2019, doi:10.1530/EDM-19-0013.
Arya VB, et al. Exceptional Diazoxide Sensitivity in Hyperinsulinaemic Hypoglycaemia Due to a Novel HNF4A Mutation. Endocrinol Diabetes Metab Case Rep. 2019 May 16;2019 PubMed PMID: 31096182.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Exceptional diazoxide sensitivity in hyperinsulinaemic hypoglycaemia due to a novel HNF4A mutation. AU - Arya,Ved Bhushan, AU - Kalitsi,Jennifer, AU - Hickey,Ann, AU - Flanagan,Sarah E, AU - Kapoor,Ritika R, Y1 - 2019/05/16/ PY - 2019/04/05/received PY - 2019/04/25/accepted PY - 2019/5/17/entrez PY - 2019/5/17/pubmed PY - 2019/5/17/medline KW - 2019 KW - Beta-hydroxybutyrate KW - Chlorothiazide KW - Diabetes KW - Diazoxide KW - Female KW - Fluid repletion KW - Glucagon KW - Glucose KW - Glucose (blood) KW - Hyperglycaemia KW - Hyperinsulinaemia KW - Hyperinsulinaemic hypoglycaemia KW - Hypoglycaemia KW - Insulin KW - May KW - Molecular genetic analysis KW - Neonatal KW - Paediatric KW - Pancreas KW - United Kingdom KW - Unusual effects of medical treatment KW - White JF - Endocrinology, diabetes & metabolism case reports JO - Endocrinol Diabetes Metab Case Rep VL - 2019 N2 - 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. SN - 2052-0573 UR - https://www.unboundmedicine.com/medline/citation/31096182/Exceptional_diazoxide_sensitivity_in_hyperinsulinaemic_hypoglycaemia_due_to_a_novel_HNF4A_mutation L2 - https://edm.bioscientifica.com/doi/10.1530/EDM-19-0013 DB - PRIME DP - Unbound Medicine ER -