Skip to main content

CASE REPORT article

Front. Endocrinol.
Sec. Pediatric Endocrinology
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1471596
This article is part of the Research Topic Perinatal and Post-Natal Life: Metabolism and Health Outcomes View all 4 articles

A Novel HNF1A variant Linked to Gestational Diabetes, Congenital Hyperinsulinism, and Diazoxide Hypersensitivity

Provisionally accepted
SURESH CHANDRAN SURESH CHANDRAN 1,2,3,4*Deepti Verma Deepti Verma 1Victor Samuel Rajadurai Victor Samuel Rajadurai 1,2,3,4Fabian Yap Fabian Yap 1,3,4*
  • 1 Department of Paediatrics, KK Women’s and Children’s Hospital, Singapore, Singapore
  • 2 Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
  • 3 Duke-NUS Medical School, Singapore, Singapore
  • 4 Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore

The final, formatted version of the article will be published soon.

    Diazoxide (DZX) remains the first-line medication for the treatment of prolonged and persistent forms of hyperinsulinemic hypoglycemia (HH). In nearly 40-50% of cases of HH, the genetic mechanism is unidentified. Almost half of the infants with permanent or genetic causes are DZX sensitive, but hypersensitivity to DZX is extremely rare, and the mechanism is poorly understood. Here, we report for the first time a case of DZX hypersensitivity in a neonate with HH who inherited a novel HNF1A variant from the mother. A term male largefor-gestational-age infant of a diabetic mother presented with early onset of severe, recurrent hypoglycemia. Critical blood samples when hypoglycemic confirmed HH. Diazoxide was initiated at conventional doses of 5 mg/kg/day, which resulted in hyperglycemia (blood glucose, 16.6 mmol/L) within 48 hours. Glucose infusion was rapidly weaned off. DZX was withheld and eventually stopped. Following 3 days of milk feeds alone with a normal glucose profile, suspecting a resolution of HH, he underwent a 6-hour fasting study and passed. While on glucose monitoring in the hospital, he again developed hypoglycemic episodes, and the critical blood samples confirmed HH. DZX was restarted at a lower dose of 3 mg/kg/day, which required further down-titration to 0.7 mg/kg/day before steady euglycemia was obtained. No more episodes of hypo or hyperglycemia occurred, and he passed a safety fasting study before discharge. Molecular genetic testing identified a novel HNF1A mutation in the mother-child dyad, whereas the father tested negative. We concluded that the HH phenotype due to this novel HNF1A mutation can be mutation-specific and require a very low dose of DZX. Clinicians should observe closely for the risk of diabetic ketoacidosis and hyperglycemic hyperosmolar state while initiating DZX therapy.

    Keywords: gestational diabetes, Infant of diabetic mother, HNF1A variant, Hypoglycemia, congenital hyperinsulinism, diazoxide hypersensitivity

    Received: 27 Jul 2024; Accepted: 04 Sep 2024.

    Copyright: © 2024 CHANDRAN, Verma, Rajadurai and Yap. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    SURESH CHANDRAN, Department of Paediatrics, KK Women’s and Children’s Hospital, Singapore, Singapore
    Fabian Yap, Department of Paediatrics, KK Women’s and Children’s Hospital, Singapore, Singapore

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.