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ABCC8 and KCNJ11 molecular spectrum of 109 patients with diazoxide-unresponsive congenital hyperinsulinism
  1. C Bellanné-Chantelot1,
  2. C Saint-Martin1,
  3. M-J Ribeiro2,
  4. C Vaury1,
  5. V Verkarre3,
  6. J-B Arnoux4,
  7. V Valayannopoulos4,
  8. S Gobrecht1,
  9. C Sempoux5,
  10. J Rahier5,
  11. J-C Fournet3,
  12. F Jaubert3,
  13. Y Aigrain6,
  14. C Nihoul-Fékété6,
  15. P de Lonlay4
  1. 1Department of Genetics, AP-HP Groupe Hospitalier Pitié-Salpétrière, Université Pierre et Marie Curie, Paris, France
  2. 2Service Hospitalier Frédéric Joliot, I2BM, CEA, Orsay, France
  3. 3Department of Pathology, AP-HP Hôpital Necker-Enfants Malades, Université Paris Descartes, Paris, France
  4. 4Reference Center for Inherited Metabolic Diseases, AP-HP Hôpital Necker-Enfants Malades, Université Paris Descartes, Paris, France
  5. 5Department of Pathology, Faculty of Medicine, University of Louvain, Brussels, Belgium
  6. 6Department of Paediatric Surgery, AP-HP Hôpital Necker-Enfants Malades, Université Paris Descartes, Paris, France
  1. Correspondence to Dr Christine Bellanné-Chantelot, Centre de Génétique Moléculaire et Chromosomique, Groupe Hospitalier Pitié Salpêtrière, 47-83 bd de l'Hôpital, 75651 Paris Cedex 13, France; christine.bellanne-chantelot{at}


Background Congenital hyperinsulinism (CHI) is characterised by an over secretion of insulin by the pancreatic β-cells. This condition is mostly caused by mutations in ABCC8 or KCNJ11 genes encoding the SUR1 and KIR6.2 subunits of the ATP-sensitive potassium (KATP) channel. CHI patients are classified according to their responsiveness to diazoxide and to their histopathological diagnosis (either focal, diffuse or atypical forms). Here, we raise the benefits/limits of the genetic diagnosis in the clinical management of CHI patients.

Methods ABCC8/KCNJ11 mutational spectrum was established in 109 diazoxide-unresponsive CHI patients for whom an appropriate clinical management is essential to prevent brain damage. Relationships between genotype and radiopathological diagnosis were analysed.

Results ABCC8 or KCNJ11 defects were found in 82% of the CHI cases. All patients with a focal form were associated with a single KATP channel molecular event. In contrast, patients with diffuse forms were genetically more heterogeneous: 47% were associated with recessively inherited mutations, 34% carried a single heterozygous mutation and 19% had no mutation. There appeared to be a predominance of paternally inherited mutations in patients diagnosed with a diffuse form and carrying a sole KATP channel mutation.

Conclusions The identification of recessively inherited mutations related to severe and diffuse forms of CHI provides an informative genetic diagnosis and allows prenatal diagnosis. In contrast, in patients carrying a single KATP channel mutation, genetic analysis should be confronted with the PET imaging to categorise patients as focal or diffuse forms in order to get the appropriate therapeutic management.

  • congenital hyperinsulinism
  • diazoxide
  • potassium channel
  • ABCC8
  • KCNJ11

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  • Competing interests None to declare.

  • Patient consent Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.