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Congenital Hyperinsulinism pp 61–69Cite as

Molecular Diagnosis of Congenital Hyperinsulinism

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Part of the book series: Contemporary Endocrinology ((COE))

Abstract

Congenital hyperinsulinism (HI) has been associated with mutations in nine genes involved in beta cell function and insulin secretion. Accurate and timely genetic diagnosis is clinically important for patients since understanding the underlying genetic cause of the disease can guide the clinician in both medical and surgical management. In children who are unresponsive to medical treatment with diazoxide and thus will require pancreatectomy, a genetic diagnosis can provide insight into the specific histological form of HI. For example, when a single recessive mutation in either ABCC8 or KCNJ11, which together encode the two subunits of the pancreatic beta cell ATP-sensitive potassium (KATP) channel , is identified, the presense of a focal lesion is predicted with 97% sensitivity. This is of great importance to the patient because resection of the lesion will likely result in a complete cure. In addition, a genetic diagnosis can provide important information on the long-term prognosis for the child in terms of lifetime diazoxide requirement or an increased risk of adult-onset diabetes. Finally, a genetic diagnosis can provide important information for families such as the recurrence risk for future children as well as identify other family members who may be at risk for hypoglycaemia. This chapter will review the genes associated with HI and will provide an insight into strategies for testing and variant interpretation as employed by two international molecular genetic laboratories that screen for this condition.

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Author information

Author notes

  1. Sarah E. Flanagan and Kara E. Boodhansingh are contributed equally to this work.

Authors and Affiliations

  1. Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK

    Sarah E. Flanagan

  2. Division of Endocrinology and Diabetes, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Kara E. Boodhansingh

  3. Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

    Emilie Lalonde & Arupa Ganguly

Authors
  1. Sarah E. Flanagan
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  2. Kara E. Boodhansingh
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  3. Emilie Lalonde
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  4. Arupa Ganguly
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Corresponding author

Correspondence to Arupa Ganguly .

Editor information

Editors and Affiliations

  1. Division of Endocrinology and Diabetes, Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania and The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Diva D. De León-Crutchlow

  2. Division of Endocrinology and Diabetes, Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania and The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Charles A. Stanley

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Flanagan, S.E., Boodhansingh, K.E., Lalonde, E., Ganguly, A. (2019). Molecular Diagnosis of Congenital Hyperinsulinism. In: De León-Crutchlow, D., Stanley, C. (eds) Congenital Hyperinsulinism. Contemporary Endocrinology. Humana Press, Cham. https://doi.org/10.1007/978-3-030-02961-6_5

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  • DOI: https://doi.org/10.1007/978-3-030-02961-6_5

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  • Publisher Name: Humana Press, Cham

  • Print ISBN: 978-3-030-02960-9

  • Online ISBN: 978-3-030-02961-6

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