Molecular Diagnosis of Congenital Hyperinsulinism

  • Sarah E. Flanagan
  • Kara E. Boodhansingh
  • Emilie Lalonde
  • Arupa GangulyEmail author
Part of the Contemporary Endocrinology book series (COE)


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.


Hyperinsulinism Genetics KATP channel 


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Sarah E. Flanagan
    • 1
  • Kara E. Boodhansingh
    • 2
  • Emilie Lalonde
    • 3
  • Arupa Ganguly
    • 3
    Email author
  1. 1.Institute of Biomedical and Clinical ScienceUniversity of Exeter Medical SchoolExeterUK
  2. 2.Division of Endocrinology and DiabetesThe Children’s Hospital of PhiladelphiaPhiladelphiaUSA
  3. 3.Department of GeneticsUniversity of Pennsylvania School of MedicinePhiladelphiaUSA

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