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CASE REPORT article

Front. Pediatr.
Sec. Pediatric Endocrinology
Volume 12 - 2024 | doi: 10.3389/fped.2024.1520871

Case Report: The Importance of Genetic Counseling for Families with Hyperinsulinism

Provisionally accepted
Victoria R Sanders Victoria R Sanders 1,2*Katherine Lord Katherine Lord 1,2,3Winnie Sigal Winnie Sigal 1,2,3Heather Mcknight Heather Mcknight 1,2N Scott Adzick N Scott Adzick 2,4Lisa J States Lisa J States 2,5Tricia Bhatti Tricia Bhatti 2,6Diva D De Leon Diva D De Leon 1,2,3
  • 1 Division of Endocrinology and Diabetes, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
  • 2 Congenital Hyperinsulinism Center, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
  • 3 Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • 4 Department of Surgery, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
  • 5 Department of Radiology, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
  • 6 Department of Pathology and Laboratory Medicine, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, United States

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

    Congenital hyperinsulinism (HI) is the most common cause of persistent hypoglycemia in infancy. Genotype-phenotype correlations directly inform medical care for patients. Understanding the genetic etiology also allows accurate genetic counseling to be provided, illustrated by two families following a diagnosis of HI. A newborn had hypoglycemia at birth and was diagnosed with focal HI due to a paternally inherited recessive ABCC8 variant. Years later the paternal half-sibling was diagnosed with HI. Testing revealed compound heterozygous ABCC8 variants, consistent with diffuse disease. Following testing, the father's partner(s) should have been offered carrier testing. However, the parents were unaware that future children could be at increased risk of HI. The second family's son was diagnosed with HI in infancy and genetic testing identified a heterozygous recessive ABCC8 variant. Parental testing revealed both parents carried this variant. Focal HI was subsequently confirmed. This family's 1/4 chance to have a child with diffuse HI was significantly higher than the 1/540 chance their child could have focal HI. Understanding the etiology of a patient's HI not only allows for appropriate medical management but has important reproductive implications for the family. Genetic counseling is an important component of the multidisciplinary care received by every family with HI.

    Keywords: hyperinsulinism1, genetic counseling2, carrier testing3, ABCC84, recurrence risk5

    Received: 31 Oct 2024; Accepted: 23 Dec 2024.

    Copyright: © 2024 Sanders, Lord, Sigal, Mcknight, Adzick, States, Bhatti and De Leon. 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: Victoria R Sanders, Division of Endocrinology and Diabetes, Children’s Hospital of Philadelphia, Philadelphia, 19104, Pennsylvania, United States

    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.